Author: Jennifer Guinan

Devon, PA, March 12, 2018 —Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty neuropsychiatric pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare and near-rare neurological and psychiatric disorders with high unmet medical needs, today reported financial results for the fourth quarter and year ended December 31, 2017 and provided an overview of recent operational highlights.

“We made significant corporate and clinical progress throughout 2017, and achieved our goal of utilizing data from three Phase 2 studies of ZYN002 to determine the direction and strategic focus of the Company,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We enter 2018 with strong momentum including having completed a positive meeting with the FDA to discuss our clinical path for ZYN002 in Fragile X syndrome. We have a refined development and commercialization strategy focused on rare and near-rare neuropsychiatric conditions, and the expectation of achieving numerous milestones in the coming year including initiations of the pivotal Fragile X syndrome study and Phase 2 studies in developmental and epileptic encephalopathies, adult refractory focal seizures, and Tourette Syndrome.”

Fourth Quarter 2017 and Recent Highlights

ZYN002 in Fragile X Syndrome (FXS)

Announced Positive Meeting with U.S. Food and Drug Administration and Plans to Conduct a Single Pivotal Study of ZYN002 in Fragile X Syndrome to Support a New Drug Application (NDA) Filing

The Company expects to initiate a pivotal study mid-year 2018 in approximately 200 pediatric and adolescent patients in the U.S., Australia and New Zealand to support an NDA for ZYN002 in FXS. The FDA and the Company are in agreement that the primary and key secondary endpoints for the study should assess observable behaviors in patients with FXS as reported by the caregiver using the validated Aberrant Behavior Checklist in Fragile X syndrome (ABC-FXS). If the pivotal trial meets its endpoints, approval for an indication encompassing the treatment of behavioral symptoms associated with Fragile X syndrome may be granted.

ZYN002 in Developmental and Epileptic Encephalopathies (DEE)

Announced Intent to Study ZYN002 in DEE; Initiation of Phase 2 Trial Expected in the First Half of 2018

DEE is a category of rare and ultra-rare, severe brain disorders manifesting with seizures or EEG abnormalities that can directly worsen cognition or behavior. The category affects ~45,000 patients in the U.S. and includes a number of syndromes, including Doose, Dravet, Lennox-Gastaut, and West, among others. The Phase 2 open label DEE study will enroll approximately 48 pediatric and adolescent patients and will help identify new indications to take into blinded placebo-controlled studies. The primary endpoints are expected to be reduction in seizures at 12 and 24 weeks. Results from the study are expected in 2019.

ZYN002 in Focal Epilepsy

Clinical Data from the STAR 1 and STAR 2 Studies of ZYN002 in Patients with Focal Seizures Presented at the 2017 Annual Meeting of the American Epilepsy Society (AES) in Washington, D.C.

Data suggest clinically meaningful responses to ZYN002, as measured by reductions in focal seizures from the baseline period of STAR 1, are correlated with longer-term use of ZYN002.

• Patients taking ZYN002 for six months  experienced a >30% median reduction in seizures from baseline;
• Patients taking ZYN002 for nine months experienced a >65% (195 mg in STAR 1 and 390 mg in STAR 2) and >48% (390 mg in STAR 1 and STAR 2) median reduction in seizures from baseline;
• In STAR 1, patients with more severe epilepsy (defined as a baseline seizure frequency of ≥15 per month) taking ZYN002 had a greater percent reduction in seizures compared to patients with severe epilepsy receiving placebo;
• ZYN002 was very well tolerated with an incidence of adverse events comparable to placebo and no clinically significant differences between the active treatment groups; and
• There were no clinically significant changes in ECGs or laboratory results in patients receiving ZYN002.

Initiation of Double-Blind, Placebo Controlled Phase 2b Clinical Trial of ZYN002 in Approximately 300 Adult Patients with Refractory Focal Epilepsy Expected in the Second Half of 2018

Learnings from the STAR 1 and STAR 2 trials provide insight into a revised Phase 2b clinical trial design. Anticipated changes to the trial include increases in (1) baseline seizure frequency, (2) patient count and (3) trial duration. In addition, the Company will stratify randomization by baseline seizure rate and gender. Zynerba also anticipates testing a higher daily dose of ZYN002 than was used in the STAR trials. The study will be conducted in sites in the U.S., Australia and New Zealand.

ZYN001 in Tourette Syndrome

Dosing Continues in the Phase 1 Program for ZYN001 Pro-drug of Tetrahydrocannabinol (THC) Delivered via Transdermal Patch; Initiation of Phase 2 Study in Patients with Tourette Syndrome (TS) Expected in the Second Half of 2018

The Company is executing on a Phase 1 program to assess ZYN001, a patent-protected, pro-drug of THC delivered via a patch. This first-in-man study is a randomized, double-blind, placebo-controlled trial designed to assess the safety, tolerability and pharmacokinetic profile of multiple formulations of ZYN001. The Company expects to complete its Phase 1 evaluation in the first half of 2018, and then move into a Phase 2 clinical trial in Tourette Syndrome late in the second half of 2018.

Corporate

Corporate Strategy Focused on Rare and Near-Rare Neuropsychiatric Disorders with High Unmet Medical Needs  

Zynerba believes that its strategic focus provides opportunities for an efficient development and commercialization strategies that may include (1) orphan drug designation for some indications; (2) access to other available regulatory designations, which, if granted, can accelerate commercial approval; (3) a targeted physician audience enabling modest commercial investments; and (4) consistent pricing across all indications. The Company also discontinued its development programs in the capital-intensive pain spaces.

Enhanced Senior Management Team

In January 2018, Liza Squires, M.D. was named Chief Medical Officer. She has over 25 years of experience in rare and neuropsychiatric disorders with companies including Aevi Genomics Medicine, Lumos Pharma, and Shire Pharmaceuticals. She also served as the Director of Pediatric Neurology for DeVos Children’s Hospital.

In March 2018, Joe Apostolico joined Zynerba as Vice President, Human Resources. Mr. Apostolico brings the Company over 30 years of broad global healthcare and pharmaceutical human resource leadership experience from his tenures with companies including Adaptimmune Therapeutics and GSK.

Fourth Quarter 2017 Financial Results

As of December 31, 2017, cash and cash equivalents were $62.5 million, compared to $31.0 million as of December 31, 2016. Research and development expenses for the fourth quarter of 2017 were $5.8 million, including stock-based compensation of $0.6 million. General and administrative expenses for the fourth quarter of 2017 were $2.4 million, including stock-based compensation expense of $0.8 million. Net loss for the fourth quarter of 2017 was $8.1 millionwith basic and diluted net loss per share of $(0.60).

On June 9, 2017, we entered into an Open Market Sales Agreement, or “at-the-market” (ATM) offering program, with Jefferies LLC, pursuant to which we may sell, from time to time, up to $50 million of our common stock. From September 28, 2017 through October 26, 2017, the Company has sold and issued 296,594 shares under its ATM program, at a weighted average selling price of $10.74 per share, for gross proceeds of $3.2 million. Net proceeds after deducting underwriting and commissions and offering expenses were $3.0 million, which were recorded in the fourth quarter and are included in the December 31, 2017 cash and cash equivalents position.

Financial Outlook

The Company believes that the cash and cash equivalent position of $62.5 million as of December 31, 2017 is sufficient to fund operations and capital requirements well into 2019.

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is a clinical-stage specialty neuropsychiatric pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare or near-rare neuropsychiatric disorders with high unmet medical needs. We are dedicated to improving the lives of people with severe health conditions by developing cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these potentially life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including Fragile X syndrome, refractory epilepsies, Tourette Syndrome, and other neuropsychiatric disorders. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
		(unaudited)
		Three months ended								Year ended
		December 31, 2017				December 31, 2016				December 31, 2017				December 31, 2016
Revenue		$	—			$	—			$	—			$	7,250
Operating expenses:
Research and development			5,828,091				4,904,363				22,806,107				16,784,626
General and administrative			2,376,413				1,780,304				10,016,902				6,430,252
Total operating expenses			8,204,504				6,684,667				32,823,009				23,214,878
Loss from operations			(8,204,504	)			(6,684,667	)			(32,823,009	)			(23,207,628	)
Other income (expense):
Interest income (expense), net			156,204				26,980				519,554				80,222
Foreign exchange gain (loss)			(70,299	)			(139,829	)			291,151				(189,497	)
Loss on dosposal of equipment			—				(99,147	)			—				(99,147	)
Total other income (expense)			85,905				(211,996	)			810,705				(208,422	)
Loss before income taxes			(8,118,599	)			(6,896,663	)			(32,012,304	)			(23,416,050	)
Income tax benefit			—				—				—				(27,543	)
Net loss		$	(8,118,599	)		$	(6,896,663	)		$	(32,012,304	)		$	(23,388,507	)
Net loss per share – basic and diluted		$	(0.60	)		$	(0.71	)		$	(2.48	)		$	(2.58	)
Basic and diluted weighted average shares outstanding			13,423,669				9,678,924				12,914,814				9,070,232
Non-cash stock-based compensation included above:
Research and development		$	562,410			$	365,072			$	2,284,866			$	1,281,108
General and administrative			817,726				522,352				3,361,986				1,988,258
Total		$	1,380,136			$	887,424			$	5,646,852			$	3,269,366

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS
		December 31, 2017				December 31, 2016
Assets
Current assets:
Cash and cash equivalents		$	62,510,277			$	30,965,791
Incentive and tax receivables			3,983,604				3,613,943
Prepaid expenses and other current assets			1,733,701				1,830,958
Total current assets			68,227,582				36,410,692
Property and equipment, net			164,527				143,382
Other assets			662,200				200
Total assets		$	69,054,309			$	36,554,274
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable		$	3,355,255			$	1,848,084
Accrued expenses			3,915,491				4,284,907
Deferred grant revenue			171,975				833,975
Total current liabilities			7,442,721				6,966,966
Deferred grant revenue, long-term			662,000				—
Total liabilities			8,104,721				6,966,966
Stockholders’ equity:
Common stock			13,554				9,995
Additional paid-in capital			138,916,900				75,545,875
Accumulated deficit			(77,980,866	)			(45,968,562	)
Total stockholders’ equity			60,949,588				29,587,308
Total liabilities and stockholders’ equity		$	69,054,309			$	36,554,274

Investor Contacts

Jim Fickenscher, CFO and VP Corporate Development
Zynerba Pharmaceuticals
484.581.7483
fickenscherj@zynerba.com

Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

 

Company Expects to Initiate Pivotal Study Mid-Year 2018 and Deliver Top-line Data in 2019

Devon, PA, March 5, 2018  – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty neuropsychiatric pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare and near-rare neurological and psychiatric disorders with high unmet medical needs, today announced the results of a positive meeting held with the U.S. Food and Drug Administration (FDA) regarding its planned development strategy for ZYN002 in Fragile X syndrome (FXS). FXS is a rare genetic developmental disability that is the leading known cause of both inherited intellectual disability and autism spectrum disorder.

ZYN002 is the first and only pharmaceutically-produced cannabidiol (CBD) formulated as a patent-protected permeation-enhanced transdermal gel. Zynerba has received U.S. Orphan Drug designation for the use of CBD as a treatment of FXS. Currently, there are no approved therapies to treat FXS or its most common symptoms.

Based on the Company’s dialogue with the FDA, the Company expects to initiate a single pivotal study mid-year 2018 to support a New Drug Application (NDA) for ZYN002 in FXS. The FDA and the Company are in agreement that the primary and key secondary endpoints for the study should assess observable behaviors in patients with FXS as reported by the caregiver using the validated Aberrant Behavior Checklist in Fragile X syndrome (ABC-FXS). If the pivotal trial meets its endpoints, approval for an indication encompassing the treatment of behavioral symptoms associated with Fragile X syndrome may be granted.

“The FDA meeting was an important milestone for us as we advance the development of ZYN002 for patients and their families suffering with the profound behavioral symptoms of Fragile X syndrome,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We are pleased with the outcome of the discussion and the guidance on trial design, and believe we now have a path forward to advance the development of ZYN002 to an NDA. We look forward to initiating the pivotal study mid-year, and potentially providing FXS patients and their families an effective and well tolerated therapy to treat the complex behavioral symptoms of Fragile X syndrome.”

Zynerba plans to initiate a pivotal 14-week randomized, double blind, placebo controlled clinical trial in approximately 200 pediatric and adolescent patients in the U.S., Australia and New Zealand. Patients will be randomized 1:1 to receive either one of two weight based doses of ZYN002, or one of two matching administrations of placebo. Zynerba anticipates initiation of this pivotal clinical trial mid-year 2018. Additional protocol details will be shared at that point. All patients will be eligible to enroll in a 12-month open label extension after completing dosing in the pivotal study.

“We believe that ZYN002 may address core behavioral symptoms of FXS and improve the quality of life for patients and their families,” said Dr. Liza Squires, Zynerba’s Chief Medical Officer. “There are currently no drugs indicated to address behavioral symptoms in the FXS population. We believe we have designed an efficient pivotal program that includes endpoints that measure clinically relevant and observable behaviors in patients with FXS, and if successful, positions us to bring the FXS community its first targeted treatment designed with patients’ symptoms in mind.”

About Fragile X syndrome
Fragile X syndrome is a rare genetic developmental disability that is the leading known cause of both inherited intellectual disability and autism spectrum disorder, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. It is the most common inherited intellectual disability in males and a significant cause of intellectual disability in females. It is caused by a mutation in the Fragile X Mental Retardation gene located on the X chromosome and leads to dysregulation of the endocannabinoid pathway including the reduction in endogenous cannabinoids (2-AG and anandamide). The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities, social anxiety and memory problems. In the US, there are about 71,000 patients suffering with FXS.

About Our Technology
Cannabinoids are a class of chemical compounds found in the Cannabis plant. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and ∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data support the potential for CBD in treating epilepsy and Fragile X syndrome, and THC has positive effects on treating symptoms of Tourette Syndrome. Zynerba is developing therapeutic medicines that utilize innovative transdermal technologies that, if successful, may allow for sustained and controlled delivery of therapeutic levels of CBD and THC. Transdermal delivery of cannabinoids may have benefits over oral dosing because it allows the drug to be absorbed through the skin directly into the bloodstream. This avoids first-pass liver metabolism, potentially enabling lower dosage levels of active pharmaceutical ingredients with a higher bioavailability and improved safety profile. Transdermal delivery also avoids the gastrointestinal tract, lessening the opportunity for GI related adverse events and the potential degradation of CBD by gastric acid into THC, which may be associated with unwanted psychoactive effects. Using an established pharmaceutical process for manufacturing, Zynerba replicates the CBD and THC found in the Cannabis plant. We believe that this will allow us to meet stringent global regulatory agencies’ standards while ensuring that we can efficiently supply the amount of product required to meet the demand of the large markets that we are targeting.

About ZYN002
Zynerba’s ZYN002 CBD gel is the first and only pharmaceutically-produced CBD formulated as a patent-protected permeation-enhanced transdermal gel and is being studied in children and adolescents with Fragile X syndrome and developmental and epileptic encephalopathies, and in adult epilepsy patients with focal seizures. ZYN002 is a clear, permeation-enhanced gel that is designed to provide controlled drug delivery transdermally with once- or twice-daily dosing.

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare or near-rare neuropsychiatric diseases with high unmet medical needs. We are dedicated to improving the lives of people with severe health conditions by developing cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these potentially life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including Fragile X syndrome, refractory epilepsies, Tourette Syndrome, and other neuropsychiatric disorders. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated.  Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Investor Contact
Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

– Focusing Strategy on Rare and Near-Rare Neurological and Psychiatric Disorders –

– Pediatric Neurologist Liza Squires, M.D. Joins as Chief Medical Officer –

– Conference Call to be Held at 8:30 AM Tomorrow, January 4, 2018 –

Devon, PA, January 3, 2018 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments, today announced that it will concentrate its focus on rare (meeting the US FDA designation of an orphan disease, affecting fewer than 200,000 people in the U.S.) and near-rare (affecting fewer than one million people in the U.S.) neurological and psychiatric (“neuropsychiatric”) disorders with high unmet medical needs. In 2018, the Company intends to develop ZYN002 in a pivotal Phase 2/3 program in Fragile X syndrome (FXS) and in Phase 2 programs in refractory epilepsies, including adult refractory focal epilepsy and developmental and epileptic encephalopathies (DEE) in pediatric and adolescent patients. Additionally, the Company plans to initiate Phase 2 development of ZYN001 in Tourette Syndrome by year end 2018.

“The decision to concentrate on rare and near-rare neurological and psychiatric disorders is driven by a number of important factors, including the compelling ZYN002 clinical data seen to date in Fragile X syndrome and refractory focal epilepsy and by the opportunities for an expedited path to approval,” said Armando Anido, Zynerba’s Chairman and Chief Executive Officer. “We believe that it also allows us to maximize the potential for ZYN002 and ZYN001 with an efficient development and commercial strategy and opportunities for consistent pricing across indications. All told, we believe we are well positioned to execute on this strategy, including having sufficient capital to fund operations well into 2019.”

2018 Anticipated Milestones
“As we head into 2018, we look forward to delivering on a number of significant corporate and clinical milestones that are important to our investors, and the patients we seek to treat,” said Anido. “We view 2018 as a year of corporate evolution for Zynerba. We plan to initiate pivotal studies for ZYN002 in FXS that will read out in 2019, initiate two new Phase 2 studies in refractory epilepsies, and initiate a Phase 2 program with ZYN001 in Tourette Syndrome. We also will continue to collect a significant amount of important data from our ongoing open-label extension studies in Fragile X syndrome and adult refractory focal epilepsy that we expect to present and/or publish during the year.”

ZYN002 Development Plans
Zynerba is currently developing ZYN002, the first and only patent-protected, pharmaceutically-produced CBD that is formulated as a permeation-enhanced gel for transdermal delivery.

• The Company has a meeting scheduled with the U.S. Food and Drug Administration during the first quarter of 2018 to discuss a pivotal program for ZYN002 in FXS, an inherited autism spectrum disorder affecting approximately 71,000 patients in the US. The Company expects to initiate the pivotal, double-blind placebo controlled clinical trial mid-year 2018. Zynerba has received U.S. Orphan Drug designation for the use of CBD as treatment of FXS;
• The Company expects to initiate an open-label study of ZYN002 in developmental and epileptic encephalopathies (DEE), a category of rare and ultra-rare, severe brain disorders manifesting with seizures or EEG abnormalities that can directly worsen cognition or behavior. The study will initiate in the first half of 2018 and will enroll approximately 48 pediatric and adolescent patients. It is designed to identify new indications to take into blinded, placebo-controlled studies;
• Zynerba intends to initiate a Phase 2B double-blind placebo controlled clinical trial of ZYN002 in adult refractory focal epilepsy, a subcategory of epilepsy impacting approximately 500,000 patients who are refractory to other anti-epileptic drugs (AED), in the second half of 2018. The design of this study will be modified from the STAR 1 trial design based on the data presented at the 2017 American Epilepsy Society meeting and additional analysis of the STAR 1 and STAR 2 data. Changes to the trial design based on these data are expected to include an increase in the number of patients enrolled, changes in randomization methodologies utilized, an increase in required baseline seizure frequency, an increase in the length of the study, and the inclusion of a higher dose of ZYN002;
• The Company will continue to generate important open label data in the ongoing 12-month FAB-C extension study in pediatric and adolescent patients with FXS and the ongoing STAR 2 18-month extension study in adult refractory focal epilepsy and plans on presenting/publishing updates in 2018;
• Zynerba is assessing the potential for ZYN002 in other rare and near-rare neuropsychiatric indications;
• Zynerba is discontinuing its investment into the capital-intensive pain space, due to inconsistency with its rare and near-rare neuropsychiatric focus. As a result, although the initial Phase 2 STOP data were encouraging, the Company has discontinued investment into the ZYN002 osteoarthritis program.

ZYN001 Development Plans
Zynerba is currently in Phase 1 development of ZYN001, the Company’s patent-protected, pro-drug of tetrahydrocannabinol (THC) delivered via a transdermal patch.

• The Company expects to complete its Phase 1 evaluation of multiple formulations of ZYN001 in the first half of 2018;
• The Company expects to take ZYN001 into a Phase 2 clinical trial in Tourette Syndrome (TS), a neurodevelopmental disorder characterized by motor and vocal tics impacting approximately 140,000 children and adolescents in the U.S., late in the second half of 2018. The National Institute of Neurological Disorders and Stroke estimate that 200,000 Americans have the most severe form of TS, and as many as one in 100 exhibit milder and less complex symptoms such as chronic motor or vocal tics.Two third-party controlled Phase 2 trials of THC in Tourette Syndrome have shown significant reduction in tics compared to placebo;
• Zynerba is assessing the potential for ZYN001 in other rare and near-rare neuropsychiatric indications;
• The Company is discontinuing its investment into the capital-intensive pain space, including its pursuit of fibromyalgia and general peripheral neuropathic pain (PNP) indications for ZYN001, due to inconsistency with its rare and near-rare neuropsychiatric focus.

Appointment of new Chief Medical Officer
To complement this concentration in rare and near-rare neuropsychiatric disorders, Liza A. Squires, MD, a pediatric neurologist, has been appointed to the newly created role of Chief Medical Officer reporting to Terri Browning Sebree. Dr. Squires will have oversight of the Company’s clinical strategy and activities, including clinical research, medical affairs, regulatory affairs, and drug safety and surveillance. Dr. Squires brings over 25 years of experience in rare and neuropsychiatric disorders to Zynerba, and was most recently the Vice President and Therapeutic Area Head of Neuroscience for Aevi Genomic Medicine, where she led neuroscience product strategy and development. She served as Chief Medical Officer for Lumos Pharma, where she developed an accelerated development strategy for an ultra-orphan population. She spent nearly 10 years at Shire Pharmaceuticals, culminating in her tenure as Vice President of R&D and Product General Manager of CNS Early Pipeline. Dr. Squires served as the Director of Pediatric Neurology for DeVos Children’s Hospital. She is a Diplomate of the American Board of Pediatrics and the American Board of Neurology and Psychiatry, with special competence in Child Neurology, and received her Medical Doctorate from the Michigan State University College of Human Medicine.

“I’m pleased to announce the addition of Dr. Liza Squires as our new Chief Medical Officer; she brings a wealth of clinical, medical, and biotechnology industry experience in pediatric neurology and rare neuropsychiatric disorders,” said Terri Browning Sebree, Zynerba’s President. “We have an excellent team at Zynerba, with a proven track record in orphan drugs, CNS disorders and transdermal delivery. Liza’s pediatric neurology background and insights will complement our team well. We welcome her to the Company and look forward to her contributions to the development of our pipeline.”

Financial Status
Zynerba believes it is well capitalized to fund operations and capital requirements well into 2019. As of September 30, 2017, the Company had a cash and cash equivalent position of $66.3 million. An additional $3.0 million in net proceeds from shares sold in September and October 2017 under its ATM program was recorded in the fourth quarter of 2017.

Conference call information
Zynerba management will host a live conference call and webcast tomorrow, January 4, 2018 at 8:30 am Eastern Time to provide a corporate update. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 2395619. To access the live webcast or the replay, visit the investor page of the Company’s website at http://ir.zynerba.com/. The webcast will be recorded and available on the Company’s website for 30 days.

About ZYN002
Zynerba’s ZYN002 CBD gel is the first and only pharmaceutically-produced CBD formulated as a patent-protected permeation-enhanced gel and is being studied in children with Fragile X syndrome and in refractory epilepsies. ZYN002 is a clear, permeation-enhanced gel that is designed to provide controlled drug delivery transdermally with once- or twice-daily dosing.

About ZYN001
ZYN001 is a synthetic pro‑drug of THC in a state-of-the-art drug-adhesive matrix transdermal patch, currently in Phase 1 clinical development. THC is a CB₁ agonist which acts at many sites along the central cannabinoid receptor system, and has been shown to be effective in the treatment of motor and vocal tics. A pro‑drug is a drug administered in an inactive or less active form and designed to enable more effective delivery, which is then converted into an active form through a normal metabolic process.

About Our Technology
Cannabinoids are a class of chemical compounds found in the Cannabis plant. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and ∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data support the potential for CBD in treating epilepsy, Fragile X Syndrome and other neuropsychiatric disorders, and THC has positive effects on treating tics. Zynerba is developing therapeutic medicines that utilize innovative transdermal technologies that, if successful, may allow for sustained and controlled delivery of therapeutic levels of CBD and THC. Transdermal delivery of cannabinoids may have benefits over oral dosing because it allows the drug to be absorbed through the skin directly into the bloodstream. This avoids first-pass liver metabolism, potentially enabling lower dosage levels of active pharmaceutical ingredients with a higher bioavailability and improved safety profile. Transdermal delivery also avoids the gastrointestinal tract, lessening the opportunity for GI related adverse events and the potential degradation of CBD by gastric acid into THC, which may be associated with unwanted psychoactive effects. Using an established chemical pharmaceutical process for manufacturing, Zynerba replicates the CBD and THC found in the Cannabis plant. We believe that this will allow us to meet stringent global regulatory agencies’ standards while ensuring that we can efficiently supply the amount of product required to meet the demand of the large markets that we are targeting.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals (NASDAQ: ZYNE) is a clinical-stage specialty neuropsychiatric pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments for rare or near-rare diseases with high unmet medical needs. We are dedicated to improving the lives of people with severe health conditions by developing cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including Fragile X syndrome, refractory epilepsies, Tourette Syndrome, and other neuropsychiatric disorders. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Zynerba Contact
Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

Media contact
Theresa Dolge
Tonic Life Communications
Office: 215-928-2748
Theresa.Dolge@toniclc.com

– Clinically Meaningful Median Reduction in Seizures Compared to Baseline of 48% to 65% Achieved with Continued ZYN002 Treatment in STAR 2 Extension Study –

Median Percent Change in Seizure Rates at Week 12 (STAR 1) and Month 3 and 6 (STAR 2)

– Data Help Clarify Protocol Design for Planned ZYN002 Phase 2 Trial in Epilepsy –

Washington, DC, December 03, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments, today is reporting new clinical data presented at the 2017 Annual Meeting of the American Epilepsy Society (AES) in Washington, DC.

In a poster presentation entitled, “Synthetic Transdermal Cannabidiol for the Treatment of Focal Epilepsy in Adults (poster #2.428),” Terence O’Brien, MD of the Royal Melbourne Hospital at The University of Melbourne presented new data from the completed Phase 2 STAR 1 (Synthetic Transdermal Cannabidiol for the Treatment of Epilepsy) study and ongoing STAR 2 18-month open label extension study evaluating ZYN002 cannabidiol (CBD) transdermal gel in patients with focal seizures. The presentation included data through nine months of total exposure to ZYN002 (three months of treatment in STAR 1 and six months in STAR 2).

The key findings include that clinically meaningful responses to ZYN002, as measured by reductions in focal seizures from the baseline period of STAR 1, are correlated with continued treatment with ZYN002. Patients who received ZYN002 (195mg during STAR 1 for three months and 390mg for six months in STAR 2) for a total of nine months achieved a median reduction in seizures of 65%. Patients who received ZYN002 (390mg for three months in STAR 1 and six months in STAR 2) achieved a 48% median reduction in seizures from baseline. In addition, ZYN002 was shown to be very well tolerated through nine months of exposure.

“These new ZYN002 data are the first of their kind, showing that focal seizures in adults may be effectively treated by a transdermal gel delivery of pharmaceutically-produced cannabidiol,” said Terri Browning Sebree, Zynerba’s President. “In this population of patients, continued treatment with ZYN002 was shown to significantly reduce seizure rates compared to baseline. Importantly, baseline seizure frequency appears to be an important indicator of response. These are important findings that will help us finalize a new trial design. We expect to outline the design, size and timing of the trial in the first quarter of 2018, and initiate the trial later in 2018.”

“The data presented this afternoon at the American Epilepsy Society meeting are exciting as they demonstrate that ZYN002 may have an effect on focal seizures in adults suffering from refractory epilepsy,” said Terence O’Brien, MD. “The epilepsy community has been eagerly awaiting data demonstrating the potential of pharmaceutically-produced cannabidiol formulated for transdermal delivery. Evidence for the efficacy of CBD-based treatments to reduce seizures in certain epilepsy populations is emerging, but there is no previous high level clinical trial evidence for focal seizures in adults. The potential for a CBD-based treatment with an optimal tolerability profile would be significant for these patients. I look forward to participating in the next clinical trial with ZYN002, and believe that this drug holds great promise for patients suffering from refractory epilepsy.”

The data presented in the poster are as follows:

Demographics and Baseline Characteristics

• Patients randomized into STAR 1 (N=188) had a median monthly seizure frequency of 10.6 (3-335) at baseline. By group, the median monthly seizure frequency at baseline was 10.5 for the placebo group, 14.0 for the ZYN002 195 mg treatment group, and 10.14 for the ZYN002 390 mg treatment group;
• Of the 188 randomized patients, 186 were analyzed for efficacy, and 174 completed the 12-week STAR 1 study;
• 171 patients (98% of STAR 1 completers) continued into STAR 2;
• Patients were taking a wide range of antiepileptic drugs (AEDs), with a median of 3.0 AEDs; use of clobazam was excluded in both the STAR 1 and STAR 2 studies.

Efficacy

• As previously disclosed on August 7, 2017, compared with baseline, after 12 weeks of blinded treatment, the change in seizure frequency did not statistically differ between placebo and both doses of ZYN002, though there was a numerical difference favoring ZYN002;
• The lack of separation of ZYN002 from placebo in STAR 1 was likely due in part to 15 (24%) placebo-treated patients who achieved at least a 50% reduction in focal seizures; 13 of these 15 patients had a relatively low baseline seizure rate (<15 focal seizures per month);
• In STAR 1, patients with more severe epilepsy (defined as a baseline seizure frequency of ≥15 per month) taking ZYN002 had a greater percent reduction in seizures compared to patients with severe epilepsy receiving placebo;
• Continued exposure to ZYN002 in STAR 2 (all patients dosed with 390 mg/day) resulted in clinically meaningful reductions in seizures:
  °  Patients taking ZYN002 for six months (three months during STAR 1 and three months in STAR 2) experienced a >30% median reduction in seizures from baseline;
  °  Patients taking ZYN002 for nine months (three months during STAR 1 and six months in STAR 2) experienced a >65% (195 mg in STAR 1 and 390 mg in STAR 2) and >48% (390 mg in STAR 1 and STAR 2) median reduction in seizures from baseline.

An infographic accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/a149a6dd-69c9-4abd-a7b5-2935e6d6504f

• A small number of patients in STAR 2 had an increase in their background AEDs; the improvements in seizure frequency observed in STAR 2 were not due to these changes to background AEDs.

Safety

• ZYN002 was very well tolerated with an incidence of adverse events comparable to placebo and no clinically significant differences between the active treatment groups;
• The safety profile of ZYN002 was consistent with previously released data from Phase 1 and Phase 2 trials;
• There were no clinically significant changes in ECGs or laboratory results in patients receiving ZYN002.

A copy of the poster presentation is currently available on the Zynerba corporate website at http://zynerba.com/publications/

About ZYN002
Zynerba’s ZYN002 CBD gel is the first and only pharmaceutically-produced CBD formulated as a patent-protected permeation-enhanced gel and is being studied in children with Fragile X Syndrome, adult epilepsy patients with focal seizures and osteoarthritis. ZYN002 is a clear, permeation-enhanced gel that is designed to provide controlled drug delivery transdermally with once- or twice-daily dosing.

About Our Technology
Cannabinoids are a class of chemical compounds found in the Cannabis plant. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and ∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data support the potential for CBD in treating epilepsy, arthritis and Fragile X Syndrome, and THC has positive effects on treating pain. Zynerba is developing therapeutic medicines that utilize innovative transdermal technologies that, if successful, may allow for sustained and controlled delivery of therapeutic levels of CBD and THC. Transdermal delivery of cannabinoids may have benefits over oral dosing because it allows the drug to be absorbed through the skin directly into the bloodstream. This avoids first-pass liver metabolism, potentially enabling lower dosage levels of active pharmaceutical ingredients with a higher bioavailability and improved safety profile. Transdermal delivery also avoids the gastrointestinal tract, lessening the opportunity for GI related adverse events and the potential degradation of CBD by gastric acid into THC, which may be associated with unwanted psychoactive effects. Using an established chemical pharmaceutical process for manufacturing, Zynerba replicates the CBD and THC found in the Cannabis plant. We believe that this will allow us to meet stringent global regulatory agencies’ standards while ensuring that we can efficiently supply the amount of product required to meet the demand of the large markets that we are targeting.

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including epilepsy, Fragile X syndrome, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Zynerba Contact
Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

Media contact
Theresa Dolge
Tonic Life Communications
Office: 215-928-2748
Theresa.Dolge@toniclc.com

Devon, PA, November 21, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments, today announced the acceptance and presentation details of a Late Breaking poster at the 2017 Annual Meeting of the American Epilepsy Society (AES) in Washington, DC, taking place December 1 through December 5, 2017.

Sunday, December 3, 2017
Poster title: “Synthetic Transdermal Cannabidiol for the Treatment of Focal Epilepsy in Adults”
Poster session: 2 
Poster number:  428
Author presentation time: 12:00PM – 2:00PM EST
Display time: 10:00AM – 4:00PM EST
Location:  Hall B, Lower Level
Abstract ID: 2.428

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including epilepsy, Fragile X syndrome, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Zynerba Contact
Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

Media contact
Theresa Dolge
Tonic Life Communications
Office: 215-928-2748
Theresa.Dolge@toniclc.com

Devon, PA, November 14, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments, today reported financial results for the third quarter ended September 30, 2017 and provided an overview of recent operational highlights.

“We announced important data during the third quarter, including remarkable Phase 2 data from our FAB-C study of ZYN002 in children and adolescents with Fragile X syndrome,” said Armando Anido, Chairman and Chief Executive Officer. “We achieved the primary endpoint and numerous secondary endpoints with statistical significance compared to baseline, and anticipate moving into a pivotal program in Fragile X in the first half of 2018. Additionally, we look forward to outlining our path forward in Epilepsy, and meeting with the FDA to discuss our OA pivotal program in the first quarter of 2018.”

Third Quarter 2017 and Recent Highlights

ZYN002 in Fragile X Syndrome (FXS)

Announced Positive Results from FAB-C Open Label Exploratory Phase 2 Clinical Trial of ZYN002 Cannabidiol (CBD) Gel in Pediatric and Adolescent Fragile X Syndrome Patients; Company Expects to Initiate Pivotal Program in the First Half of 2018

A total of 20 patients were enrolled into the 12-week open label Phase 2 FAB-C trial to evaluate ZYN002 cannabidiol (CBD) gel in pediatric and adolescent patients with FXS.

• The study successfully met its primary endpoint, achieving a 46% improvement (p<0.0001) in the total score of Anxiety, Depression, and Mood Scale (ADAMS) at week twelve compared to baseline;
• The results of the secondary endpoints reinforce those demonstrated in the ADAMS. For example, ZYN002 also achieved clinically meaningful and statistically significant improvements compared to baseline in all measures of the Aberrant Behavior Checklist for Fragile X (ABC-FXS), which address the key symptoms of FXS including social avoidance, temper tantrums, repetitive movements, and hyperactivity;
• ZYN002 was shown to be extremely well tolerated, and the safety profile was consistent with previously released data from clinical trials;
• Thirteen (13) of the 18 patients completing the study have enrolled into the 52-week open label extension and remain in the trial;
• The Company anticipates that it will meet with the U.S. Food and Drug Administration (FDA) in the first quarter of 2018 to discuss the results of the study and next steps, including a pivotal program expected to initiate in the first half of 2018; and
• The FDA has granted orphan-drug designation to Zynerba for the use of CBD for the treatment of FXS.

ZYN002 in Osteoarthritis

Announced Important Results from Phase 2 STOP Clinical Trial for ZYN002 CBD Gel in Adult Osteoarthritis Patients; Study Achieved Key Secondary Endpoints with Statistical Significance

Three hundred and twenty (320) patients were randomized into the double-blind, placebo-controlled Phase 2 STOP trial in osteoarthritis of the knee.

• Statistically significant results were achieved for a number of secondary endpoints, though the study did not achieve its primary endpoint of change from baseline in the weekly mean of the 24-hour average worst pain score at week 12;
• Importantly, the composite responder analysis (defined as a ≥30 percent reduction in worst average daily pain scores and a ≥20 percent improvement in the WOMAC physical function score) for 250 mg daily of ZYN002 4.2% CBD gel achieved statistical significance (p=0.016). This composite responder endpoint is consistent with the FDA guidelines requiring the use of both pain and function endpoints in pivotal osteoarthritis programs;
• ZYN002 was shown to be extremely well tolerated and the safety profile was consistent with previously released data from clinical trials; and
• Zynerba anticipates that it will meet with the FDA in the first quarter of 2018 to discuss the results of the study. The Company expects to initiate a pivotal Phase 2/3 program in 2018.

ZYN002 in Focal Seizures

Announced Results from Phase 2 STAR 1 Clinical Trial for ZYN002 CBD Gel in Adult Epilepsy Patients with Focal Seizures

A total of 188 patients were randomized in the Phase 2 STAR 1 double-blind, placebo-controlled clinical trial in adult patients with refractory epilepsy.

• ZYN002 did not demonstrate a statistically significant reduction of focal seizures during the treatment period compared to the baseline period for either the high or low dose cohorts compared to placebo;
• The Company believes that the study failed to achieve its endpoints primarily due to a bimodal distribution of patient responses on placebo; approximately 24% of patients receiving placebo achieved >50% reductions in focal seizures, while the other approximately 76% of placebo patients showed no improvement or worsening of focal seizures; and
• ZYN002 was shown to be extremely well tolerated and the safety profile was consistent with previously released data from the Phase 1 trials.

Dosing Continues in the Phase 2 STAR 2 Open-Label Extension Trial for ZYN002 CBD Gel in Adult Epilepsy Patients; Clinically Meaningful Responses Achieved in Patients on ZYN002 for at least 6 Months

As of November 13, 2017, one hundred (100) patients remain in the STAR 2 open label trial, designed to evaluate long-term safety and tolerability of ZYN002 CBD gel across a range of doses. In the open-label extension study, patients are receiving ZYN002 for up to 52 weeks.

• Eighty-nine (89) patients have reached six months of drug exposure in STAR 2; and
• Clinically meaningful reductions in seizures (>50%) have been observed in patients on ZYN002 for at least six months.

Data from the ZYN002 epilepsy program have been accepted for poster presentation at the 2017 American Epilepsy Society (AES) Meeting.

Further analysis of data from STAR 1 and STAR 2 will clarify the study design and inclusion / exclusion criteria ahead of a new Phase 2 clinical study in epilepsy. The Company expects to outline its path forward in epilepsy in the first quarter of 2018.

ZYN001 Phase 1 Evaluation

Dosing Continues in the Phase 1 Program for ZYN001 Pro-drug of Tetrahydrocannabinol (THC) Delivered via Transdermal Patch

Dosing is underway in a Phase 1 program to assess ZYN001, a patent-protected, pro-drug of THC delivered via a patch. This first in man study is a randomized, double-blind, placebo-controlled Phase 1 trial. The safety, tolerability and pharmacokinetic profile of a single dose of ZYN001 versus placebo is initially being evaluated. Several formulations and patch wear times ranging from 24 hours to 7 days will be assessed in up to 48 healthy subjects. Based on results from the single dose portion of this trial, two formulations will be evaluated in multiple patch applications for 14 days in up to 32 healthy subjects who will be randomized 3:1 to ZYN001 or placebo. Results from this study are now expected in the first half of 2018. These data will inform the planned Phase 2 program for ZYN001, now expected to initiate in 2018.

Third Quarter 2017 Financial Results

As of September 30, 2017, cash and cash equivalents were $66.3 million, compared to $70.2 million as of June 30, 2017. Research and development expenses for the third quarter of 2017 were $5.8 million, including stock-based compensation of $0.6 million. General and administrative expenses for the third quarter of 2017 were $2.8 million, including stock-based compensation expense of $1.1 million. Net loss for the third quarter of 2017 was $8.3 million with basic and diluted net loss per share of $0.63.

Recent Equity Financing

On June 9, 2017, we entered into an Open Market Sales Agreement, or “at-the-market” (ATM) offering program, with Jefferies LLC, pursuant to which we may sell, from time to time, up to $50 million of our common stock. From September 28, 2017 through October 26, 2017, the Company has sold and issued 296,594 shares under its ATM program, at a weighted average selling price of $10.74 per share, for gross proceeds of $3.2 million. Net proceeds after deducting underwriting and commissions and offering expenses were $3.0 million. None of the proceeds were settled prior to September 30, 2017, and therefore the cash for the sale of these common shares will be recorded in the fourth quarter.

Financial Outlook

The Company believes that the cash and cash equivalent position of $66.3 million as of September 30, 2017 is sufficient to develop five Phase 3-ready programs and initiate at least one pivotal program and fund operations and capital requirements into 2019.

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including Fragile X syndrome, epilepsy, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
(Unaudited)
		Three months ended								Nine months ended
		September 30, 2017				September 30, 2016				September 30, 2017				September 30, 2016
Revenue		$	—			$	—			$	—			$	7,250
Operating expenses:
Research and development			5,753,764				4,504,097				16,978,016				11,880,264
General and administrative			2,795,839				1,493,461				7,640,489				4,649,948
Total operating expenses			8,549,603				5,997,558				24,618,505				16,530,212
Loss from operations			(8,549,603	)			(5,997,558	)			(24,618,505	)			(16,522,962	)
Other income (expense):
Interest income			161,930				22,747				363,350				53,243
Foreign exchange gain (loss)			76,468				(6,270	)			361,450				(49,668	)
Total other income (expense)			238,398				16,477				724,800				3,575
Loss before income taxes			(8,311,205	)			(5,981,081	)			(23,893,705	)			(16,519,387	)
Income tax benefit			—				—				—				(27,543	)
Net loss		$	(8,311,205	)		$	(5,981,081	)		$	(23,893,705	)		$	(16,491,844	)
Net loss per share – basic and diluted		$	(0.63	)		$	(0.67	)		$	(1.87	)		$	(1.86	)
Basic and diluted weighted average shares outstanding			13,098,914				8,912,508				12,743,332				8,865,854
Non-cash stock-based compensation included above:
Research and development		$	591,898			$	292,385			$	1,722,456			$	916,036
General and administrative			1,130,745				513,019				2,544,260				1,465,906
Total		$	1,722,643			$	805,404			$	4,266,716			$	2,381,942

ZYNERBA PHARMACEUTICALS, INC.
CONSOLIDATED BALANCE SHEETS
(Unaudited)
	September 30, 2017				December 31, 2016
Assets
Current assets:
Cash and cash equivalents	$	66,251,286			$	30,965,791
Incentive and tax receivables		3,617,956				3,613,943
Prepaid expenses and other current assets		3,010,144				1,830,958
Total current assets		72,879,386				36,410,692
Property and equipment, net		190,370				143,382
Other assets		200				200
Total assets	$	73,069,956			$	36,554,274
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable	$	3,116,100			$	1,848,084
Accrued expenses		4,479,292				4,284,907
Deferred grant revenue		833,975				833,975
Total current liabilities		8,429,367				6,966,966
Stockholders’ equity:
Common stock		13,257				9,995
Additional paid-in capital		134,489,599				75,545,875
Accumulated deficit		(69,862,267	)			(45,968,562	)
Total stockholders’ equity		64,640,589				29,587,308
Total liabilities and stockholders’ equity	$	73,069,956			$	36,554,274

Investor Contacts
Jim Fickenscher, CFO and VP Corporate Development
Zynerba Pharmaceuticals
484.581.7483
fickenscherj@zynerba.com

Will Roberts, VP Investor Relations and Corporate Communications
Zynerba Pharmaceuticals
484.581.7489
robertsw@zynerba.com

Devon, PA, November 7, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE) a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments, today announced that Armando Anido, Chairman and Chief Executive Officer, will provide a company overview at two investor conferences in November:

• Stifel 2017 Healthcare Conference on Tuesday, November 14, 2017 at 5:00 p.m. ET at the Lotte New York Palace in New York, NY
• 29th Annual Piper Jaffray Healthcare Conference on Tuesday, November 28, 2017 at 10:30 a.m. at the Lotte New York Palace in New York, NY

To listen to a webcast of either presentation live, please visit the Investor Relations page of www.zynerba.com. A replay of the webcast will be available for 90 days following the conclusion of the event.

About Zynerba Pharmaceuticals, Inc.
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including epilepsy, Fragile X syndrome, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Investor Contact
Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

ZYN002 successfully met the primary endpoint and showed clinically meaningful improvements

Zynerba to host conference call and webcast today, September 28 at 8:30 am ET

Devon, PA, September 28, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative pharmaceutically-produced transdermal cannabinoid treatments, today announced positive top line results from an open label exploratory Phase 2 FAB-C (Treatment of Fragile X Syndrome Anxiety and Behavioral Challenges with CBD) clinical trial evaluating ZYN002 cannabidiol (CBD) gel in pediatric and adolescent patients with Fragile X syndrome (FXS). The study successfully met its primary endpoint, achieving a 46% improvement (p<0.0001) in the total score of Anxiety, Depression, and Mood Scale (ADAMS) at week twelve compared to baseline. ZYN002 also achieved clinically meaningful improvements in all measures of the Aberrant Behavior Checklist for Fragile X (ABC-FXS), which address the key symptoms of FXS including social avoidance, temper tantrums, repetitive movements, and hyperactivity.

“The data from the FAB-C trial are very exciting and demonstrate that ZYN002 may have a profound effect on improving many of the most disabling symptoms of Fragile X, such as anxiety and difficult behaviors,” said Steven Siegel, MD, PhD Professor and Chair, Psychiatry and Behavior Sciences, Keck School of Medicine of USC. “Fragile X is a challenging genetic autism spectrum disorder, with complex symptomatology that significantly impacts patients and their families. Many children with Fragile X and their families struggle with the lack of approved drugs to safely treat their symptoms. This study suggests that ZYN002 is ready for the next phase of development, and I believe that this drug holds great promise as a potential treatment for these very difficult-to-treat symptoms.”

With these data, Zynerba anticipates that it will meet with the U.S. Food and Drug Administration (FDA) in the first half of 2018 with the goal of moving quickly into a pivotal Phase 2/3 program in pediatric and adolescent patients with FXS in 2018. The FDA has granted Zynerba Orphan Drug designation for the use of CBD as treatment of patients with FXS. Orphan Drug designation is granted to novel drugs that treat a rare disease or condition affecting fewer than 200,000 patients in the U.S., and provides benefits including a seven-year period of U.S. marketing exclusivity upon marketing approval for the designated indication and may provide a rapid path to market authorization.

“We are thrilled with the positive clinical results of ZYN002 in the FAB-C trial; it is a major step forward for the hundreds of thousands of patients worldwide with Fragile X who currently have no approved therapeutic options to treat their symptoms,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “The clinically meaningful improvements in Fragile X symptoms and the excellent tolerability seen in the FAB-C trial are compelling. These data will allow us to discuss the pathway to approval in a meeting with the FDA, which we expect to take place during the first half of 2018. I want to thank the patients, families, physicians, study coordinators, and the Zynerba team for their support of this important study.”

“The symptoms of Fragile X can be overwhelming to a patient and caregiver, so I’m very enthusiastic about the responses to ZYN002 that we saw during this study,” said Honey Heussler, FRACP, Associate Professor at Children’s Health Queensland, Medical Director Child Development and lead investigator in the FAB-C study. “These data are extremely promising, particularly the improvements in anxiety, social avoidance, and irritability as measured by scales including ADAMS, ABC-FXS, and PARS-R. Tolerability is essential in these patients, so I’m very pleased to see that ZYN002 was well tolerated in Fragile X patients.”

Study Design
Twenty patients (3:1 males) aged 6 to 17 years of age (mean = 10.7) with Fragile X as confirmed by molecular documentation of FMR1 full mutation were enrolled in the open label FAB-C study. ZYN002 was added on to other medications being administered. The first six weeks of the study were designed to titrate dosing in patients. Dosing was initiated at 50 mg daily and could be increased to 250 mg daily. Weeks 7 through 12 of the study was a maintenance period where patients were treated at the dose established at week six. At the completion of the study, patients could enter an open label extension study for up to 12 months.

Top-line data: Primary endpoint
The primary endpoint for the trial was the change in the total score of the Anxiety, Depression, and Mood Scale (ADAMS) from baseline to week 12. The ADAMS is a 28-item scale designed to assess general anxiety, social avoidance, compulsive behavior, manic/hyperactive behavior, and depressed mood. It has been validated in patients with FXS.

Results for the primary endpoint are summarized as follows:

	Baseline		Week 12		Change in Score		% improvement			p Value
ADAMS: Total Score	33.4		18.1		-14.1		45.81	%		<0.0001

The subscales of ADAMS are as follows:

	Baseline		Week 12		Change in Score		% Improvement			p Value
ADAMS:  General Anxiety Subscale	10.0		4.6		-4.8		54.00	%		<0.0001
ADAMS:  Social Avoidance Subscale	10.2		4.8		-5.1		52.94	%		0.0002
ADAMS: Compulsive Behavior Subscale	2.8		1.4		-1.2		50.00	%		0.0262
ADAMS: Manic / Hyperactive Behavior Subscale	9.4		6.1		-2.7		35.11	%		0.0003
ADAMS: Depressed Mood Subscale	2.8		2.0		-0.9		28.57	%		0.1417

Top-line data: Secondary endpoints
The Company evaluated multiple secondary endpoints including the Aberrant Behavior Checklist – FXS Specific (ABC-FXS), a Clinical Global Impression of Improvement (CGI-I), the Pediatric Anxiety Rating Scale (PARS-R), Visual Analog Scales for Anxiety, Hyperactivity and Tantrum/Mood Lability, the Vineland Adaptive Behavior III, a Quality of Sleep measurement and the Pediatric Quality of Life (PedsQL™). The results of the secondary endpoints reinforce the results demonstrated in the ADAMS.

Results from the ABC-FXS are summarized as follows:

	Baseline		Week 12		Change in Score		% improvement			p Value
ABC: Irritability – “Has Temper Tantrums”	18.2		10.6		-7.1		41.76	%		0.0096
ABC: Hyperactivity – “Disrupts Group Activities”	14.5		9.7		-4.1		33.10	%		0.0194
ABC: Socially Unresponsive/Lethargic –  “Does Not Pay Attention”	8.7		4.1		-5.1		52.87	%		0.0034
ABC: Social Avoidance – “Seeks Isolation”	5.1		2.3		-2.8		54.90	%		0.0005
ABC: Stereotypy –  “Repetitive Movements”	7.9		3.2		-4.9		59.49	%		0.0006
ABC: Inappropriate Speech – “Repeats Words or Phrases”	6.1		3.5		-2.4		42.62	%		0.0018

Safety data
ZYN002 was shown to be very well tolerated, and the safety profile was consistent with previously released data from clinical trials. Two patients discontinued due to worsening of pre-existing eczema. Four other patients experienced an adverse event. No adverse events were considered severe. No patient experienced drug-related GI events during the 12-week treatment period, and no THC was detected in the plasma. Thirteen of the 18 patients who completed the study have enrolled in the open label extension.

Conference call information
Zynerba management will host a live conference call and webcast today at 8:30 am Eastern Time to discuss the results of this clinical trial. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 90858811. To access the live webcast or the replay, visit the investor page of the Company’s website at http://ir.zynerba.com/. The webcast will be recorded and available on the Company’s website for 30 days.

About Fragile X syndrome
Fragile X syndrome is an autism spectrum disorder affecting 1 in 4,000 males and 1 in 8,000 females. It is the most common inherited intellectual disability in males and a significant cause of intellectual disability in females. It is caused by a mutation in the Fragile X Mental Retardation gene located on the X chromosome and leads to dysregulation of the endocannabinoid pathway including the reduction in endogenous cannabinoids (2-AG and anandamide). The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities, social anxiety and memory problems. In the US, there are about 71,000 patients suffering with FXS.

About Our Technology
Cannabinoids are a class of chemical compounds found in the Cannabis plant. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and ∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data support the potential for CBD in treating epilepsy, arthritis and Fragile X Syndrome, and THC has positive effects on treating pain. Zynerba is developing therapeutic medicines that utilize innovative transdermal technologies that, if successful, may allow for sustained and controlled delivery of therapeutic levels of CBD and THC. Transdermal delivery of cannabinoids may have benefits over oral dosing because it allows the drug to be absorbed through the skin directly into the bloodstream. This avoids first-pass liver metabolism, potentially enabling lower dosage levels of active pharmaceutical ingredients with a higher bioavailability and improved safety profile. Transdermal delivery also avoids the gastrointestinal tract, lessening the opportunity for GI related adverse events and the potential degradation of CBD by gastric acid into THC, which may be associated with unwanted psychoactive effects. Using an established chemical pharmaceutical process for manufacturing, Zynerba replicates the CBD and THC found in the Cannabis plant. We believe that this will allow us to meet stringent global regulatory agencies’ standards while ensuring that we can efficiently supply the amount of product required to meet the demand of the large markets that we are targeting.

About ZYN002
Zynerba’s ZYN002 CBD gel is the first and only pharmaceutically-produced CBD formulated as a patent-protected permeation-enhanced gel and is being studied in children with Fragile X Syndrome, osteoarthritis and in adult epilepsy patients with focal seizures. ZYN002 is a clear, permeation-enhanced gel that is designed to provide controlled drug delivery transdermally with once- or twice-daily dosing.

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including epilepsy, Fragile X syndrome, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Zynerba Contacts
Jim Fickenscher, CFO and VP Corporate Development
484.581.7483
fickenscherj@zynerba.com

Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com 

Media Contact
Theresa Dolge
Tonic Life Communications
Office: 215-928-2748
Theresa.Dolge@toniclc.com

Devon, PA, September 6, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative transdermal pharmaceutically-produced cannabinoid treatments, today announced that Armando Anido, Chairman and Chief Executive Officer, will present a company overview at the upcoming Rodman & Renshaw 19th Annual Global Investment Conference at the Lotte New York Palace, New York on Tuesday, September 12, 2017 at 9:10 a.m. ET.

The Company will also be participating in investor meetings at the 15th Annual Morgan Stanley Global Healthcare conference at the Grand Hyatt Hotel, New York on Wednesday September 13, 2017.

To listen to a webcast of the Rodman & Renshaw presentation live, please visit the Investor Relations page of www.zynerba.com. A replay of the webcast will be available for 90 days following the conclusion of the event.

About Zynerba Pharmaceuticals, Inc. 
Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these potentially life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including epilepsy, Fragile X syndrome, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Statement on Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, including the Company’s expectations regarding the completion, timing and size of the option exercise, the Company’s anticipated proceeds therefrom and other statements containing the words “anticipate,” “believe,” “estimate,” “upcoming,” “plan,” “target”, “intend,” “expect” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, risks and uncertainties associated with market conditions and the satisfaction of customary closing conditions related to the proposed offering, as well as other risks and uncertainties discussed in the Risk Factors set forth in the Company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC and in other filings the Company makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent the Company’s views only as of the date of this press release. Important factors could cause our actual results to differ materially from those indicated or implied by forward-looking statements, and as such we anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Investor Contact
Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

Zynerba to host conference call and webcast today, August 14 at 8:30 am ET

Devon, PA, Aug. 14, 2017 – Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), a clinical-stage specialty pharmaceutical company dedicated to developing and commercializing innovative transdermal pharmaceutically-produced cannabinoid treatments, today reported top line results from its Phase 2 STOP (Synthetic Transdermal Cannabidiol for Treatment of Knee Pain due to Osteoarthritis) clinical trial evaluating ZYN002 (cannabidiol [CBD] gel). The study did not meet its primary endpoint of reduction from baseline in the weekly mean of the 24-hour average worst pain score at week 12 for either dose. However, statistically significant results were achieved for a number of secondary endpoints. Importantly, the composite responder analysis (defined as a ≥30 percent reduction in worst average daily pain scores and a ≥20 percent improvement in the WOMAC physical function score) for 250 mg daily of ZYN002 4.2% CBD gel achieved statistical significance (p=0.016). A trend toward statistical significance was observed in other secondary endpoints.

“Many osteoarthritis patients using currently available medicines do not experience relief from pain and improved physical functioning, or cannot tolerate them due to side effects,” said Daniel Clauw, M.D., Professor of Pain Management and Anesthesiology at the University of Michigan, and Director of the Chronic Pain and Fatigue Research Center. “The STOP trial results are encouraging and suggest that ZYN002 can play an important role in impacting the pain and impaired physical function associated with osteoarthritis, with a well-tolerated safety profile. I am particularly impressed with the composite analysis result which accounts for both pain and physical function. I believe that ZYN002 may provide a promising treatment option for OA, and I look forward to participating in future studies.”

“The results from this study are very encouraging and for the first time suggest that CBD has a clinically meaningful impact in osteoarthritis, which affects approximately 31 million people in the United States,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “In recent years, as the opioid epidemic has worsened, doctors, patients and their families have continued to emphasize the need for new, non-opioid pain medications, especially those with more favorable side effect profiles than NSAIDs or COX-2 inhibitors.”

Anido continued, “Data from the STOP trial will help shape future studies with ZYN002 in osteoarthritis. We will request an end of Phase 2 meeting with the U.S. Food and Drug Administration, which we believe will take place before the end of this year, and plan to move quickly to our pivotal Phase 3 program for ZYN002 in OA. I want to thank the participating patients, physicians, study coordinators, and the Zynerba team for their support of this important study.”

Three hundred and twenty (320) patients aged 41 to 78 years of age with confirmed osteoarthritis of the knee were randomized in the double-blind, multi-center STOP trial. Patients who completed the one-week washout and the seven-to-10-day baseline phase were randomized 1:1:1 to receive either 250 mg of ZYN002 4.2% CBD gel daily, 500 mg of ZYN002 daily, or placebo, for 12 weeks. Enrolled patients had a mean worst knee pain score of 6.9 on a scale of 1 to 10 during baseline.

• Primary Endpoint Data: Across all participants, patients on 250 mg of ZYN002 daily achieved a 2.64 mean reduction from baseline in average worst knee pain scores at week 12; patients on 500 mg of ZYN002 daily achieved a 2.83 mean reduction from baseline in average worst knee pain scores at week 12; and patients on placebo achieved a 2.37 mean reduction from baseline in average worst knee pain scores at week 12. These results were not statistically significant.
• Secondary Endpoint Data: Statistically significant results were achieved for a number of key secondary endpoints, including the composite responder analysis for 250 mg of ZYN002 daily (p=0.016), and the responder rate based on ≥30% reduction in worst pain severity at week 8 for 250 mg of ZYN002 daily (p=0.037). A trend toward statistical significance was observed in other secondary endpoints.
• Post Hoc Analysis (Gender): Men on 250 mg of ZYN002 daily achieved a 1.65 mean reduction from baseline in average worst knee pain scores at week 4 compared to a 1.19 mean reduction from baseline in men on placebo (p=0.156); a 2.30 mean reduction from baseline in average worst knee pain scores at week 8 compared to a 1.56 mean reduction from baseline in men on placebo (p=0.066); and a 2.68 mean reduction from baseline in average worst knee pain scores at week 12 compared to a 1.70  mean reduction from baseline in men on placebo (p=0.049). Females had a higher placebo rate and did not achieve significance in the endpoint.
• Post Hoc Analysis (Pain Severity): In an evaluation of patients with a baseline pain score of ≥7, there were 101 patients on ZYN002 and 48 patients in the placebo arm at baseline. Patients on ZYN002 achieved a 2.17 mean reduction from baseline in average worst knee pain scores at week 4 compared to a 1.6 mean reduction from baseline in patients on placebo (p=0.029); a 3.02 mean reduction from baseline in average worst knee pain scores at week 8 compared to a 2.22 mean reduction from baseline in patients on placebo (p=0.054); and a 3.29 mean reduction from baseline in average worst knee pain scores at week 12 compared to a 2.52 mean reduction from baseline in patients on placebo (p=0.086).
• Safety Data: ZYN002 was shown to be very well tolerated and the safety profile was consistent with previously released data from clinical trials. Of the patients in the safety database, 50% (n=106) of the patients on ZYN002 had at least one treatment emergent adverse event, compared to 42% (n=45) of patients on placebo. There were only two treatment emergent/treatment related adverse events that exceeded 3% of the patients on ZYN002 and were greater than placebo: application site dryness (3.8%, n=8; placebo 0.9%, n=1) and headache (3.3%, n=7; placebo 1.9%, n=2). There was one (0.5%) treatment related serious adverse event on ZYN002 and three (2.8%) treatment related serious adverse events reported on placebo. Discontinuation from the study was 22.5% (n=48) for patients on ZYN002 and 33.6% (n=36) for patients on placebo. There were twelve (5.6%) patients that discontinued due to adverse events on ZYN002 and 8 (7.5%) that discontinued due to adverse events on placebo.
• Pharmacokinetic Data: ZYN002 500 mg and 250 mg daily dose median plasma concentrations were dose proportional, with the 500 mg dose levels being approximately two times the plasma concentration of the 250 mg dose.

Additional ongoing studies of ZYN002

Zynerba is also currently evaluating the utility of ZYN002 in its exploratory Phase 2 FAB-C (Treatment of Fragile X Syndrome Anxiety and Behavioral Challenges with CBD) study in children with Fragile X syndrome (FXS). Top line data from this study are expected by the end of September 2017. In addition, epilepsy patients with focal seizures continue to be dosed in the 52-week STAR 2 (Synthetic Transdermal Cannabidiol for the Treatment of Epilepsy) open label extension trial.

Conference call information

Zynerba management will host a live conference call and webcast today at 8:30 am Eastern Time to discuss the results of this clinical trial. The call can be accessed by dialing (866) 573-0180 (U.S. and Canada) or (430) 775-1345 (international) and referencing conference ID 70071749. To access the live webcast or the replay, visit the investor page of the Company’s website at http://ir.zynerba.com/. The webcast will be recorded and available on the Company’s website for 30 days.

About Osteoarthritis

Osteoarthritis is a degenerative joint disease that leads to wear and tear of the joints and affects the cartilage, joint lining, ligaments and bone. It is the most common form of joint disease and tends to occur most often in the hand joints, spine, hips, knees and great toes. It is characterized by the breakdown of the joint cartilage, bony changes in the joints and deterioration of the tendons and ligaments leading to pain and inflammation of the joint lining. Approximately 31 million patients in the US suffer from osteoarthritis.

About Our Technology

Cannabinoids are a class of chemical compounds found in the Cannabis plant. The two primary cannabinoids contained in Cannabis are cannabidiol, or CBD, and ∆9-tetrahydrocannabinol, or THC. Clinical and preclinical data support the potential for CBD in treating epilepsy, arthritis and Fragile X Syndrome, and THC has positive effects on treating pain. Zynerba is developing therapeutic medicines that utilize innovative transdermal technologies that, if successful, may allow for sustained and controlled delivery of therapeutic levels of CBD and THC. Transdermal delivery of cannabinoids may have benefits over oral dosing because it allows the drug to be absorbed through the skin directly into the bloodstream. This avoids first-pass liver metabolism, potentially enabling lower dosage levels of active pharmaceutical ingredients with a higher bioavailability and improved safety profile. Transdermal delivery also avoids the gastrointestinal tract, lessening the opportunity for GI related adverse events and the potential degradation of CBD by gastric acid into THC, which may be associated with unwanted psychoactive effects. Using an established chemical pharmaceutical process for manufacturing, Zynerba replicates the CBD and THC found in the Cannabis plant. We believe that this will allow us to meet stringent global regulatory agencies’ standards while ensuring that we can efficiently supply the amount of product required to meet the demand of the large markets that we are targeting.

About ZYN002

Zynerba’s ZYN002 CBD gel is the first and only pharmaceutically-produced CBD formulated as a patent-protected permeation-enhanced gel and is being studied in adult epilepsy patients with focal seizures, in osteoarthritis and in children with Fragile X Syndrome. ZYN002 is a clear, permeation-enhanced gel that is designed to provide controlled drug delivery transdermally with once- or twice-daily dosing.

About Zynerba Pharmaceuticals, Inc.

Zynerba Pharmaceuticals (NASDAQ:ZYNE) is dedicated to improving the lives of people with severe health conditions where there is a high unmet medical need by developing and commercializing pharmaceutically-produced transdermal cannabinoid medicines designed to meet the rigorous efficacy and safety standards established by global regulatory agencies. Through the discovery and development of these life-changing medicines, Zynerba seeks to improve the lives of patients battling severe, chronic health conditions including epilepsy, Fragile X syndrome, osteoarthritis, fibromyalgia and peripheral neuropathic pain. Learn more at www.zynerba.com and follow the Company on Twitter at @ZynerbaPharma.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for ZYN002 or ZYN001 from the U.S. Food and Drug Administration(FDA) or foreign regulatory authorities; even if ZYN002 or ZYN001 are approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. In addition, the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the success, cost and timing of the Company’s product development activities, studies and clinical trials; the success of competing products that are or become available; the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Zynerba Contacts
Jim Fickenscher, CFO and VP Corporate Development
484.581.7483
fickenscherj@zynerba.com

Will Roberts, VP Investor Relations and Corporate Communications
484.581.7489
robertsw@zynerba.com

Media Contact
Theresa Dolge
Tonic Life Communications
Office: 215-928-2748
Theresa.Dolge@toniclc.com