On November 14, 2018 CohBar, Inc. (NASDAQ: CWBR), a clinical stage biotechnology company developing mitochondria based therapeutics (MBTs) to treat age-related diseases, reported financial results for the third quarter ended September 30, 2018, and provided a business update (Press release, CohBar, NOV 14, 2018, View Source [SID1234531310]).

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"As we previously discussed, we are moving forward with our plan to address the mild but persistent injection site reactions observed in our Phase 1 clinical trial of CB4211, under development for NASH and obesity," said Simon Allen, Chief Executive Officer of CohBar. "We will be sharing this plan shortly with the FDA, and look forward to the agency’s timely feedback and resuming clinical activities as expeditiously as possible."

"This first groundbreaking study of a mitochondria based therapeutic in humans will help inform us not only for the development of CB4211, but also for the development of other potential therapeutics from our large portfolio of novel peptides. We continue to believe in the potential of MBTs to treat a broad range of age-related diseases with large-population indications, including type 2 diabetes, cancer, neurodegenerative disease and cardiovascular disease," Mr. Allen concluded.

Third Quarter and Recent Business Highlights:

Clinical Study Update for CB4211. On November 5, 2018, the company announced the temporary suspension of its ongoing Phase 1 clinical study of CB4211, its lead MBT candidate under development as a potential treatment for non-alcoholic steatohepatitis (NASH) and obesity, in order to address mild injection site reactions that have been unexpectedly persistent. The company has a plan to address the persistent reactions and is seeking feedback from the FDA before resuming the clinical study.

Partnership with LifeSci Advisors. CohBar engaged LifeSci Advisors LLC ("LifeSci"), a leading New York-based investor relations consultancy serving life science companies, to implement a comprehensive investor outreach program that will include analyst and investor targeting/outreach, non-deal roadshows, corporate communications, and Key Opinion Leader (KOL) events in the field of mitochondria based therapeutics and age-related diseases.

Investment and Scientific Community Outreach. During the third quarter, CohBar’s CEO Simon Allen presented an overview of the Company and its clinical development program at the Bio Investor Forum. Additionally, company management met with investors during the H.C. Wainwright 20th Annual Global Investment Conference.
During the third quarter, CohBar’s founders, Dr. Pinchas Cohen and Dr. Nir Barzilai, continued to be recognized as international leaders in the study of aging, age-related diseases and mitochondrial science.

Dr. Cohen co-authored a number of papers published in scientific journals during the quarter including "Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans," in Nature Scientific Reports; "Chronic Treatment with the Mitochondrial Peptide Humanin Prevents Age-related Myocardial Fibrosis in Mice," in American Journal of Heart Circulation Physiology; "Characterizing the Protective Effects of SHLP2, a Mitochondrial-Derived Peptide, in Macular Degeneration," in Nature Scientific Reports; and "Mitochondrial biology and prostate cancer ethnic disparity," Carcinogenesis. Dr. Cohen also received a major grant from the National Institutes of Health recognizing his ground-breaking work in the field of mitochondrial science entitled, "Humanin is an AD resilience factor through its interaction with APOE4."

Dr. Barzilai delivered a keynote speech at the Aging Cell Conference in Sitges, Spain and co-authored a number of scientific papers published during the quarter including: "Aging as a Biological Target for Prevention and Therapy," in JAMA; "A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: Report from the TAME Biomarkers Workgroup," in Geroscience; "Targeting Senescence," in Nature Medicine; "APOE Alleles and Extreme Human Longevity," Journals of Gerontology; "40 Years of IGF1: The Jekyll and Hyde of the Aging Brain," in Journal of Molecular Endocrinology; "Late-Life Targeting of the IGF1 Receptor Improves Healthspan and Lifespan in Female Mice," in National Communications.
Third Quarter 2018 Financial Highlights

Cash and Investments. CohBar had cash and investments of $24,223,712 on September 30, 2018, compared to $8,452,459 on December 31, 2017.

R&D Expenses. Research and development expenses were $3,435,509 in the three months ended September 30, 2018, compared to $2,316,454 in the prior year quarter. The increase was primarily due to the costs of our clinical activities and a net increase in stock-based compensation related to performance equity grants that vested within the current year quarter, offset by a decrease in costs related to the timing of IND-enabling activities incurred in the prior year period.

G&A Expenses. General and administrative expenses were $1,061,709 for the three months ended September 30, 2018, compared to $549,505 in the prior year quarter. The increase in general and administrative expenses was primarily due to an increase in stock-based compensation related to performance equity grants that vested within the current year quarter, the costs associated with new grants made since the prior year period and an increase in directors fees in the current quarter.

Net Loss. For the three months ended September 30, 2018, net loss was $4,613,042, or $0.11 per basic and diluted share, compared to a net loss of $2,861,107, or $0.07 per basic and diluted share, for the three months ended September 30, 2017.

Details for Conference Call

Date: November 14, 2018
Time: 5:00 p.m. Eastern Time

- Dial-in U.S. and Canada: (888) 394-8218
- Dial-in International: (323) 701-0225
- Conference ID Number: 1659879

We kindly request that you call into the conference audio approximately 10 minutes before the start time so that we can begin promptly.

An audio replay of the call will be available beginning at 8:00 p.m. Eastern Time on November 14, 2018, through 11:59 p.m. Eastern Time on December 5, 2018. To access the recording please dial (844) 512-2921 in the U.S. and Canada, or (412) 317-6671 internationally, and reference Conference ID# 1659879. The audio replay will also be available at www.cohbar.com from November 14 through December 5, 2018.

About CB4211
CohBar’s lead program is based on CB4211, a first-in-class mitochondria based therapeutic (MBT) that has demonstrated significant therapeutic potential in preclinical models of nonalcoholic steatohepatitis (NASH) and obesity. CB4211 is a novel and improved analog of MOTS-c, a naturally occurring mitochondrial-derived peptide (MDP) which was discovered in 2012 by CohBar founder Dr. Pinchas Cohen and his academic collaborators and has been shown to play a significant role in the regulation of metabolism. In July 2018, CB4211 entered a Phase 1a/1b clinical trial which includes a potential activity readout relevant to NASH and obesity. In November 2018, the company announced the temporary suspension of the trial to address mild injection site reactions that were unexpectedly persistent. NASH has been estimated to affect as many as 12% of adults in the U.S., and there is currently no approved treatment for the disease.

On November 14, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of two Type II variation applications to the European Medicines Agency (EMA) seeking approval for the expanded use of IMBRUVICA (ibrutinib) (Press release, Johnson & Johnson, NOV 14, 2018, View Source [SID1234531468]). One application seeks to include use of ibrutinib in combination with obinutuzumab in previously untreated adults with chronic lymphocytic leukaemia (CLL) and to add long-term follow-up data from the existing label studies RESONATETM (PCYC-1112) and RESONATETM-2 (PCYC-1115). The second is for use of ibrutinib plus rituximab for the treatment of previously untreated and relapsed/refractory adults with Waldenström’s macroglobulinemia (WM).

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"Today’s news brings us one step closer to potentially offering ibrutinib in new combinations for patients where unmet needs still persist," said Dr. Catherine Taylor, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. "Ibrutinib continues to demonstrate clinical benefit over the long term for a broad
group of patients living with blood cancer, and we look forward to working with relevant authorities to secure approval of these new combinations."

Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company. The CLL submission is supported by positive results from the Phase 3 iLLUMINATE (PCYC1130) study which investigated ibrutinib in combination with obinutuzumab versus
chlorambucil plus obinutuzumab in patients with newly diagnosed CLL.

1 Study findings from iLLUMINATE will also be featured as an oral presentation (abstract #691), whilst further analysis of RESONATETM and RESONATETM-2 results in comparison with real-world evidence databases (abstract #4427) will be included at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place in San Diego next month.1,2 A supplemental New Drug Application (sNDA) which was also recently submitted to the U.S. Food and Drug Administration (FDA) received Priority Review.

2 In WM, the submission is supported by data from the Phase 3 iNNOVATE (PCYC-1127) study evaluating ibrutinib in combination with rituximab, versus rituximab with placebo, in patients with previously untreated and relapsed/refractory WM.

3 Follow-up efficacy and safety findings from the iNNOVATE study will also be presented at ASH (Free ASH Whitepaper) 2018 (abstract
#149).

4 In August 2018, the FDA approved ibrutinib in combination with rituximab for the treatment of WM based on the data from iNNOVATE.

5 Additional information about both studies can be found at www.ClinicalTrials.gov (NCT02264574 and NCT02165397).
6,7
#ENDS#

About ibrutinib
Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.8 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.9 Ibrutinib is currently approved in Europe for the following uses:10

 Chronic lymphocytic leukaemia (CLL): As a single agent for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.

 Mantle cell lymphoma (MCL): Adult patients with relapsed or refractory mantle cell MCL.

 Waldenström’s macroglobulinemia (WM): Adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemoimmunotherapy.

The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea, rash, and pyrexia.10

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About CLL
CLL is typically a slow-growing blood cancer of the white blood cells.11 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year with rates amongst men and women approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.

12 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.13
CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years, according to the stage of disease.14 The disease eventually progresses in the majority of patients, and patients are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.
3
About Waldenström’s macroglobulinemia
Waldenström’s macroglobulinemia (WM) is a rare form of non-Hodgkin’s lymphoma (NHL).15 It causes overproduction of a protein called monoclonal immunoglobulin M (IgM) antibody, which causes a thickening of the blood.
16 Incidence rates among men and women in Europe are approximately 7.3 and 4.2 per million persons, respectively.17 The causes of WM are unknown, with it typically affecting older adults and being slightly more
common in men than women.15,17

On November 14, 2018 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that data from Phase I clinical trials of ADCT-402 (loncastuximab tesirine) and ADCT-301 (camidanlumab tesirine) have been selected for oral and poster presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which is being held December 1-4 in San Diego (Press release, ADC Therapeutics, NOV 14, 2018, View Source [SID1234596073]).

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Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, "We look forward to sharing updated data from our first-in-human clinical trials of ADCT-402 and ADCT-301 in multiple subtypes of lymphoma at the 2018 ASH (Free ASH Whitepaper) Annual Meeting. Interim data show that ADCT-402, which targets CD19, has demonstrated durable single-agent anti-tumor activity in patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma who have failed other therapies or have no available treatment options. In addition, new data on ADCT-301 highlight the CD25-targeting ADC’s impressive overall and complete response rates in heavily pretreated patients with classical Hodgkin lymphoma, as well as its encouraging clinical activity in T-cell lymphoma."

Oral Presentations

Title: Interim Results from the First-in-Human Clinical Trial of Adct-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Abstract Number: 398
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: New Agents
Date and Time: Sunday, December 2, 2018; 12:15 p.m. PT
Location: Marriott Marquis San Diego Marina, Pacific Ballroom 20
Presenter: John Radford, MD, FRCP, Manchester Academic Health Centre, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK

Title: Phase 1 Study of Adct-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Classical Hodgkin Lymphoma
Abstract Number: 928
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Hodgkin Lymphoma: Chemotherapy and Response Adapted Approaches
Date and Time: Monday, December 3, 2018; 5:15 p.m. PT
Location: San Diego Convention Center, Room 6F
Presenter: Mehdi Hamadani, MD, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI

Poster Presentations

Title: Safety and Efficacy of Adct-402 (Loncastuximab Tesirine), a Novel Antibody Drug Conjugate, in Relapsed/Refractory Follicular Lymphoma and Mantle Cell Lymphoma: Interim Results from the Phase 1 First-in-Human Study
Abstract Number: 2874
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster II
Date and Time: Sunday, December 2, 2018; 6-8 p.m. PT
Location: San Diego Convention Center, Hall GH
Presenter: Paolo Caimi, MD, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH

Title: Adct-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based CD25-Targeting Antibody Drug Conjugate, in a Phase 1 Study of Relapsed/Refractory Non-Hodgkin Lymphoma Shows Activity in T-Cell Lymphoma
Abstract Number: 1658
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster I
Date and Time: Saturday, December 1, 2018; 6:15-8:15 p.m. PT
Location: San Diego Convention Center, Hall GH
Presenter: Graham P. Collins, MB, BS, DPhil, Oxford University Hospitals, NHS Trust, Oxford, UK

ADCT-402 is currently being evaluated in three clinical trials, including a pivotal trial in patients with relapsed or refractory diffuse large B-cell lymphoma. ADCT-301 is being evaluated in three clinical trials. To learn more about the company’s ADC programs, visit ADC Therapeutics’ Booth #117 located in the Exhibit Hall of the San Diego Convention Center.

For more information about the ASH (Free ASH Whitepaper) Annual Meeting, please visit View Source

About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (NCT03589469). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.

About ADCT-301

ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. The intra-tumor release of its PBD warhead may cause bystander killing of neighboring tumor cells. In addition, the PBD warhead will

trigger immunogenic cell death, which in turn will strengthen the immune response against tumor cells. ADCT-301 is being evaluated in ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235), as well as a Phase Ib clinical trial in solid tumors (NCT03621982).

On November 14, 2018 Neuralstem, Inc. (Nasdaq: CUR), a biopharmaceutical company focused on the development of nervous system therapies based on its neural stem cell and small molecule technologies, reported its financial results for the third quarter ended September 30, 2018 (Press release, Neuralstem, NOV 14, 2018, View Source [SID1234531311]).

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"During the third quarter of 2018 we have made progress with our programs, have taken steps to strengthen the balance sheet, and, perhaps most importantly, have determined how we will focus our efforts moving forward," said Jim Scully, Interim Chief Executive Officer of Neuralstem. "We believe that proceeds from our recent offering, combined with our efforts to reduce cash burn, will allow us to pursue key development initiatives that will be detailed in the coming weeks."

Clinical Highlights

In August, NSI-189 received from FDA the orphan designation for treatment of Angelman Syndrome. Angelman Syndrome (AS) is a rare congenital genetic disorder caused by a lack of function in the UBE3A gene on the maternal 15th chromosome. It affects approximately one in 15,000 people – about 500,000 individuals globally. Symptoms of AS include developmental delay, lack of speech, seizures, and walking and balance disorders. Patients with AS may never walk or speak and require life-long care. Life expectancy is normal which places a significant burden on patients and caregivers. There are currently no FDA-approved therapies for the treatment of Angelman syndrome.

In July, the company announced initiation of a Phase 2 clinical trial to further evaluate NSI-566 in ischemic stroke. This follows the positive results of the open-label Phase 1 stroke study disclosed in a 2018 ISSCR (International Society for Stem Cell Research) abstract on June 23, 2018. The Phase 2 study is a randomized, double-blind, sham-surgery controlled study. It is intended to further test the safety and efficacy of NSI-566 to reverse paralysis in stroke patients with half of their body partially paralyzed. The trial is taking place at BaYi Brain Hospital in Beijing, China, and commenced on August 1, 2018.

In October, the company announced publication of a manuscript in Scientific Reports showing that transplantation of NSI-532.IGF1 mitigates disease pathology and improves cognition in a mouse model of Alzheimer’s Disease. The study was performed at the University of Michigan by a team led by Dr. Eva Feldman, Director of the Program for Neurology Research and Discovery, and Research Director of the University of Michigan ALS Center of Excellence. NSI-532.IGF1 is the first candidate from the NSI-532 program, a second-generation cell therapy program which combines neural stem cells with neuroprotective proteins.
Corporate Highlights

In October, the company completed a registered direct offering of its securities which resulted in gross proceeds to Neuralstem of $2.1 million. Neuralstem intends to use the proceeds from this offering to further its clinical and preclinical programs, and for general working capital.
Financial Results for the Quarter Ended September 30, 2018

Cash Position and Liquidity: At September 30, 2018, cash and investments was $5.7 million as compared to $7.1 million at June 30, 2018. The $1.4 million decrease reflects a loss for the period, which was somewhat ameliorated by management’s cost reduction efforts. The company expects its existing cash, cash equivalents and short-term investments to fund its operations, based on its current operating plans, into the second quarter of 2019.

Operating Loss: Operating loss for the third quarter ended September 30, 2018 was $2.1 million compared to a loss of $2.6 million for the comparable period of 2017. The reduction in loss is attributed to reduced clinical development activity and management efforts to reduce overall expenses.

Net Loss: Net loss for the third quarter ended September 30, 2018 was $1.8 million, or $0.12 per share (basic), compared to a loss of $0.1 million, or $0.01 per share (basic), for the comparable period of 2017. The increase in net loss was primarily due to the non-cash gains related to the change in the fair value of our liability classified warrants in 2017, partially offset by a decrease in our operating loss.

Research and Development Expenses: The $0.9 million of research and development expenses for the quarter ended September 30, 2018 represents a 35% decrease over the comparable period of 2017. This decrease was primarily attributable to a decrease in personnel and facility expenses, and a decrease in clinical trial and related costs due to the completion of our NSI-189 Phase 2 clinical trial.

General and Administrative Expenses: The $1.2 million of general and administrative expenses for the third quarter ended September 30, 2018 represents a 2% decrease over the comparable period of 2017. This decrease was primarily attributable to lower payroll and related expenses due to corporate restructuring and cost reduction efforts coupled with a decrease in non-cash share-based compensation expense which was offset by an increase in tax and insurance expenses and consulting and professional fees.

On November 14, 2018 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the plenary presentation of updated ZW25 clinical data by Murali Beeram, MD, a clinical investigator at the START Center for Cancer Care, San Antonio, Texas (Press release, Zymeworks, NOV 14, 2018, View Source [SID1234531312]). Data from Zymeworks’ ongoing multi-center Phase 1 study showed single agent ZW25, a bispecific antibody, induced anti-tumor activity and was well tolerated in heavily pretreated patients with a variety of HER2-expressing cancers.

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"Today we report, for the first time, the durability of ZW25’s anti-tumor activity," said Ali Tehrani, Ph.D., President and CEO of Zymeworks. "With a median of over six months of progression-free survival in these heavily pretreated patients, these data further support our previously-communicated clinical strategy which includes registration-enabling studies for single-agent ZW25 in gastrointestinal-related cancers where the unmet need is so great worldwide."

ZW25 Clinical Results Presented Today

The plenary presentation includes all 24 gastroesophageal and other cancer patients treated at the Phase 2 recommended dose, of which 17 were response-evaluable (defined as having measurable disease and at least one tumor restaging) at the time of data cut-off. Of these 17 patients, eight had gastroesophageal cancers, four had colorectal cancer and five had other HER2-expressing cancers including gall bladder, cholangiocarcinoma, cervical, fallopian tube and salivary gland. The participants in the study were heavily pretreated with a median of three prior cancer treatments.

The overall disease control rate (DCR), which includes patients with partial responses and stable disease was 82%. There were seven partial responses (41%), seven stable disease (41%) and three progressive disease (18%). The median progression-free survival (mPFS) in all 24 patients was 6.21 months (95% CI 1.94-9.33).

"To observe this level of activity across so many different tumor types is quite compelling," said Murali Beeram, MD. "These were heavily pretreated patients who had essentially run out of therapeutic options, so for them to respond so favorably is indeed encouraging."

In the eight gastroesophageal cancer patients, who had a median of four prior systemic treatments, the response rate was 50%. In the four colorectal and five other HER2-expressing cancer patients the response rate was 33%. Anti-tumor activity was assessed per RECIST every eight weeks.

In the study, ZW25 was well tolerated. All treatment-related adverse events were Grade 1 or 2 with the exception of one patient with Grade 3 fatigue, and no treatment-related serious adverse events were seen. There were no Grade 4 or 5 adverse events. The most common adverse events (25% or greater) were diarrhea, infusion reaction and nausea.

"The favorable tolerability we have seen with ZW25 supports its use as both a single agent and in combination with approved anti-cancer agents," said Diana Hausman, MD, Zymeworks’ Chief Medical Officer. "We are excited to be advancing ZW25’s development and have plans to explore its efficacy in a number of tumor types, including gastroesophageal and breast cancer."

Plenary Presentation Details

The presentation is part of the Symposium on Molecular Targets and Cancer Therapeutics sponsored by the European Organization for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

Title: "Single Agent Activity of ZW25, a HER2-Targeted Bispecific Antibody, in HER2-Expressing Gastroesophageal and Other Cancers"

Session: Proffered papers, Plenary Session 2, Abstract 6

Time: Wednesday November 14, 3:45 pm GMT

Location: Auditorium

About the Trial

Zymeworks’ adaptive Phase 1 study has three parts. Enrollment in the first portion of the study (the dose-escalation phase) has been completed. The recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and is evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

About ZW25

ZW25 is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function and has led to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Orphan Drug Designation to ZW25 for the treatment of both gastric and ovarian cancers.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving them the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering and degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug-resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life, and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity with the potential to significantly reduce drug development costs and timelines.