On March 12, 2020 Tyligand Bioscience, Ltd., a leader in small molecule drug discovery and development, and Context Therapeutics LLC, a clinical stage biopharmaceutical company focused on hormone driven cancers, reported the signing of collaboration agreements for the development, manufacturing, registration and future commercialization of onapristone extended release (ER) (Press release, Tyligand Bioscience, MAR 12, 2020, View Source [SID1234644992]).

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Onapristone ER is currently being evaluated in patients with progesterone receptor positive (PR+) ovarian and endometrial cancers in the ongoing Phase 2 ONWARD 220 clinical trial. Initiation of additional Phase 2 clinical trials in ER+, PR+, HER2- breast cancer and endometrial cancers are planned for mid-2020.

Under the terms of the agreements, Tyligand will be solely responsible for the design and optimization of a novel manufacturing process for onapristone ER to meet Context’s development and future commercialization needs, and standards for quality, safety and cost. Upon completion of specific performance-based milestones, Tyligand will be granted the exclusive right and will be solely responsible for the development and commercialization of onapristone ER in China, Hong Kong and Macau (the "Territory"), and Context will be eligible to receive royalties on net sales of onapristone ER in the Territory. Context will retain rest of world rights to commercialize onapristone ER.

"We are thrilled to partner with Tyligand as we accelerate onapristone ER’s Phase 2 evaluation and prepare for Phase 3," said Martin Lehr, CEO of Context. "Tyligand is renowned for its expertise in process development and has strong networks with manufacturing and clinical capabilities in China and the U.S. Partnering with Tyligand will enable Context to optimize and efficiently scale our manufacturing and clinical capacity to support the evaluation and future commercialization of onapristone ER, our experimental oral therapy, to address the unmet need in treating patients with PR+ cancers."

"Even with the major advances in cancer therapies in recent years, treatment options for patients with hormone driven cancers remain limited," said Tony Zhang, CEO of Tyligand."Onapristone ER has the potential to be the first-in-class therapeutic agent specifically targeting progesterone receptors and the best-in-class treatment option for breast, endometrial and ovarian cancers. We are proud to partner with Context to develop onapristone ER and make this innovative medicine ultimately more accessible for patients around the world."

On March 12, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents designed to activate immune response to cancers, reported that the U.S. Food and Drug Administration (FDA) has granted Agenus Fast Track designation for investigation of balstilimab [PD-1] in combination with zalifrelimab [CTLA-4] for the treatment of patients with relapsed or refractory metastatic cervical cancer (Press release, Agenus, MAR 12, 2020, View Source [SID1234555452]). This designation was based on comprehensive data that support the potential for balstilimab and zalifrelimab to address a significant unmet medical need. Agenus expects to file 2 BLAs this year for accelerated approval of the combination of balstilimab and zalifrelimab and balstilimab monotherapy in metastatic cervical cancer.

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"We are pleased that balstilimab and zalifrelimab have been granted Fast Track designation by FDA in recognition of the high unmet medical need in second line cervical cancer. The Fast Track designation confers important benefits, including the potential eligibility for a Priority Review," said Dr. Jennifer Buell, President and COO, Agenus. "We are excited about the prospect of making these novel agents available to women who suffer from metastatic cervical cancer. We look forward to continuing to work with FDA as we advance new treatment options for patients with cancer."

Agenus has reported updated data from a pre-planned interim analysis revealing robust and durable activity of balstilimab and zalifrelimab in patients with relapsed or refractory metastatic cervical cancer. The data demonstrated 26.5% objective response rates (ORR) (4 CRs, 5 PRs, 8 SD) which are durable (median not yet reached) in an all-comer, non-biomarker selected population of patients with refractory cervical cancer who have failed prior platinum chemotherapy with or without bevacizumab.

Fast Track designation is granted by the FDA for products that are intended for the treatment of serious or life-threatening disease or conditions, which demonstrate the potential to address an unmet medical need. The designation offers the opportunity for frequent interactions with the FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval, as well as eligibility for rolling submission of a Biologic Licensing Application (BLA).

On March 12, 2020 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing novel small molecule therapeutics to treat unmet needs in autoimmunity and cancer, reported its fourth quarter and year end 2019 financial results and corporate highlights (Press release, Kezar Life Sciences, MAR 12, 2020, View Source [SID1234555482]).

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"2019 marked several key milestones for Kezar, and I’m grateful for our team’s skill and hard work moving both of our programs forward. Our selective immunoproteasome inhibitor, KZR-616, entered Phase 2 trials in five different autoimmune diseases of high unmet need, building upon encouraging data from our ongoing Phase 1b study. We also nominated KZR-261, the first clinical candidate from our protein secretion program, and expect an IND filing in early 2021", said John Fowler, Chief Executive Officer. "This year we look forward to sharing updates from the Phase 1b portion of our MISSION study, as well as an interim analysis from our MARINA trial in AIHA and ITP. Finally, after our successful financing last month, we have a strong cash position that takes us beyond all of our KZR-616 Phase 2 readouts as well as data with KZR-261 in multiple tumor types."

Recent Clinical and Business Highlights

KZR-616 – Selective Immunoproteasome Inhibitor

MISSION Study

The Phase 1b/2 MISSION study in systemic lupus erythematosus (SLE) patients with and without nephritis is currently ongoing.

Additional data from the Phase 1b portion of MISSION will be presented during various medical conferences throughout the course of 2020.

The Phase 2 portion of MISSION is a randomized, placebo-controlled, double-blind trial to evaluate the safety and efficacy of KZR-616 in patients with active proliferative lupus nephritis. The primary endpoints of this portion of the MISSION trial are safety and tolerability. Secondary and exploratory endpoints include pharmacokinetics (PK), pharmacodynamics (PD), biomarker assessments and additional measures of efficacy. This trial includes four treatment arms evaluating KZR-616 administered subcutaneously once weekly for 24 weeks at dose levels of 30 mg, 45 mg and 60 mg, compared to placebo. The trial is designed to enroll up to 64 patients.

MARINA Study

The Phase 2 MARINA study in patients with autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia (ITP) is currently ongoing.

MARINA is a Phase 2 randomized, dose-blind, multicenter trial designed to evaluate the safety, tolerability, efficacy, PK and PD of KZR-616 in patients with active AIHA or ITP. Patients with AIHA or ITP will be randomized to receive either 30 mg or 45 mg of KZR-616 subcutaneously once weekly for 13 weeks, followed by 12 weeks of follow-up. The trial is designed to enroll up to 40 patients. Kezar believes that whole blood RNASeq data from the Phase 1b portion of MISSION, which showed a decrease in multiple inflammatory gene signature and prolonged increase in erythropoietic gene signatures in SLE patients, support the broad potential anti-inflammatory activity of KZR-616 and therapeutic potential in patients with AIHA.

PRESIDIO Study

The Phase 2 PRESIDIO study in patients with polymyositis (PM) or dermatomyositis (DM) is currently ongoing.

PRESIDIO is a Phase 2 randomized, placebo-controlled, double-blind, crossover, multicenter trial to evaluate the safety, tolerability, efficacy, PK and PD of KZR-616 in patients with active PM or DM. During the 32-week treatment period, patients receive either 45 mg of KZR-616 or placebo subcutaneously once weekly for 16 weeks followed by a crossover to the other treatment arm for an additional 16 weeks. The trial is designed to enroll up to 24 patients. Kezar believes that KZR-616 has the potential to be developed into a treatment for patients with DM and PM, which is in-part supported by preclinical data in a mouse model of PM and DM that demonstrated immunoproteasome inhibition and improved muscle function.

KZR-261 – Protein Secretion Program

Research and discovery efforts targeting the protein secretion pathway have progressed significantly, and this novel program and pathway was featured in four separate presentations during two major medical and scientific conferences in 2019: the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition (ASH) (Free ASH Whitepaper).

KZR-261, our first oncology clinical candidate and a first-in-class protein secretion inhibitor, has demonstrated broad anti-tumor activity in preclinical models of both solid and hematologic malignancies. Kezar anticipates filing an Investigational New Drug (IND) application for a Phase 1 study of KZR-261 in solid tumors in the first quarter of 2021.

Business Update

On February 4, 2020, Kezar completed an underwritten public offering of 18,965,385 shares of its common stock, which includes the full exercise of the underwriters’ option, and pre-funded warrants to purchase 2,884,615 shares of its common stock at an exercise price of $0.001 per share. The public offering price of the common stock was $2.60 per share and the public offering price of each pre-funded warrant was $2.599 per underlying share. The gross proceeds from the public offering were approximately $56.8 million, before deducting underwriting discounts and offering expenses.

Financial Results

Cash, cash equivalents and marketable securities totaled $78.2 million as of December 31, 2019, compared to $107.4 million as of December 31, 2018. The decrease in cash, cash equivalents and marketable securities was primarily attributable to cash used by the company in operations to advance its clinical stage programs as well as preclinical research and development.

Research and development expenses for the fourth quarter of 2019 increased by $2.7 million to $7.4 million compared to $4.7 million in the fourth quarter of 2018. Full year R&D expenses increased by $9.2 million in 2019 compared to 2018. This increase was primarily related to advancing the KZR-616 clinical program in multiple indications and the protein secretion preclinical program.

General and administrative expenses for the fourth quarter of 2019 increased by $0.8 million to $2.6 million compared to $1.8 million in the fourth quarter of 2018. Full year G&A expenses increased by $3.4 million in 2019 compared to 2018. The increase was primarily due to an increase in personnel expenses and costs related to operating as a public company.

Net loss for the fourth quarter of 2019 was $9.6 million, or $0.50 per basic and diluted common share, compared to a net loss of $5.8 million, or $0.30 per basic and diluted common share, for the fourth quarter of 2018. Net loss for 2019 was $35.1 million, or $1.84 per basic and diluted common share, compared to $23.2 million, or $2.26 per basic and diluted common share, in 2018.

Total shares outstanding were 19.2 million as of December 31, 2019. Additionally, there were outstanding options to purchase 3.1 million shares of common stock at a weighted average exercise price of $7.19 per share as of December 31, 2019.

About KZR-616

KZR-616 is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Phase 1a clinical trial results in healthy volunteers provide evidence that KZR-616 potentially avoids adverse effects caused by currently marketed non-selective proteasome inhibitors, which Kezar believes prevent them from being utilized as a chronic treatment in autoimmune disorders. Phase 2 trials are underway for the treatment of lupus nephritis (MISSION study), autoimmune hemolytic anemia and immune thrombocytopenia (MARINA study), and dermatomyositis and polymyositis (PRESIDIO study).

About KZR-261

KZR-261, a novel, first-in-class protein secretion inhibitor, is the first clinical candidate to be nominated from Kezar’s research and discovery efforts targeting protein secretion pathways. KZR-261 is a broad-spectrum anti-tumor agent that acts through direct interaction and inhibition of Sec61 activity. The compound was discovered at Kezar through a robust medicinal chemistry campaign in which several

scaffolds were progressed through the company’s proprietary platform evaluating Sec61 modulation. As a result, Kezar has established a broad library of protein secretion inhibitors. KZR-261 has demonstrated several encouraging properties that lead to its potential to be an anti-cancer agent for the treatment of solid and hematologic malignancies. IND-enabling activities are currently underway, and an IND application in solid tumors is expected to be filed in the first quarter of 2021.

On March 12, 2020 Dendreon Pharmaceuticals, a commercial-stage biopharmaceutical company and pioneer in the development of immunotherapy, reported findings from a sub-analysis of data from its PROCEED registry comparing overall survival (OS) in African American (AA) and Caucasian (CAU) men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with PROVENGE (sipuleucel-T) in a real-world treatment setting (Press release, Dendreon, MAR 12, 2020, View Source [SID1234555513]).

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When comparing PSA-matched AA men to CAU men with a baseline PSA less than or equal to the median (29.48 ng/mL), AA men in the PROCEED registry demonstrated a median OS of over 4.5 years (54.3 months) versus over 2.7 years (33.4 months) for CAU men – an improvement of 20.9 months and a 48% relative risk reduction in death.1,2

"Racial differences in the effectiveness of treatments in mCRPC are well documented," said Oliver Sartor, M.D., co-lead author of the publication, associate dean for oncology at Tulane University School of Medicine and medical director of the Tulane Cancer Center. "The high percentage of AA men enrolled in PROCEED compared to other trials provided a unique opportunity to evaluate the effectiveness of immunotherapy in extending survival in this patient population."

The PROCEED registry enrolled nearly 2,000 patients with mCRPC who received PROVENGE between 2011 and 2014 in everyday treatment settings, and followed them for three years. Approximately 12% of patients enrolled in PROCEED were AA. This analysis compared OS in a subset of AA patients (n=107) and CAU patients (n=222) matched by baseline PSA.3

"Black men tend to present with aggressive prostate cancer and have twice the mortality rate as compared to white men," said Andrew J. Armstrong, M.D., co-lead author of the publication, professor of medicine at Duke University School of Medicine and member of the Duke Cancer Institute. "However, in the context of immunotherapy for men with mCRPC, we observe that black men have significantly improved overall survival as compared to similar white men. While we do not yet understand the reasons for this improved survival by self-identified race, these data provide evidence to support the early use of sipuleucel-T immunotherapy regardless of race in order to improve long-term survival."

PROCEED evaluated the real-world use of PROVENGE in men with asymptomatic or minimally symptomatic mCRPC. These data were published online in Prostate Cancer and Prostatic Diseases (PCAN), a peer-reviewed Nature Research journal. The publication in PCAN is the first time these sub-group data have been published in a peer-reviewed journal.

"These findings add to the growing body of published clinical evidence that PROVENGE extends life in men with mCRPC and underscore its added effectiveness in African American men," said Bruce A. Brown, M.D., chief medical officer at Dendreon. "No other prostate cancer treatment has shown this level of added benefit in African American men with mCRPC, so these findings are exciting."

About the PROCEED Registry

PROCEED (NCT01306890) was a multicenter, open-label, observational registry conducted at urology and medical oncology clinics in private practice and academic sites. PROCEED enrolled 1,976 patients with mCRPC, of whom 1,902 received PROVENGE between 2011 and 2014 in everyday treatment settings. Of these, approximately 12% were African American. In the entire PROCEED population, patients were followed for a median of 46.6 months. Their median age was 72 years and their median baseline PSA was 15.0 ng/mL. The sub-analysis published in PCAN compared OS in a subset of African American patients (n=219) and Caucasian patients (n=438) matched by baseline PSA.

About Prostate Cancer in African American Men

Prostate cancer is the most frequently occurring non-cutaneous cancer among men in the United States and is second only to lung cancer among the leading causes of cancer-related deaths. In 2020, an estimated 191,930 new cases of prostate cancer will be diagnosed in the United States and 33,330 men will die from the disease.4

African American men have the highest prostate cancer incidence rate of any racial or ethnic group in the world.5 In the United States, the risk of prostate cancer is 74% higher in black men than non-Hispanic white men.6 The incidence of prostate cancer is about 60% higher in blacks than in whites for reasons that remain unclear.4 Prostate cancer death rates in blacks are more than double those of every other racial and ethnic group in the United States.4

About PROVENGE (sipuleucel-T)

PROVENGE is the only FDA-approved immunotherapy made from a patient’s own immune cells for the treatment of prostate cancer. More than 30,000 men have been prescribed PROVENGE, and it has been clinically proven to extend life for certain men in advanced stages of the disease.

INDICATION

PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION

Acute Infusion Reactions: Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

Thromboembolic Events: Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.

Vascular Disorders: Cerebrovascular events (hemorrhagic/ischemic strokes and transient ischemic attacks) and cardiovascular disorders (myocardial infarctions) have been reported following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

Handling Precautions: PROVENGE is not tested for transmissible infectious diseases.

Concomitant Chemotherapy or Immunosuppressive Therapy: Chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. Concurrent use of immune-suppressive agents may alter the efficacy and/or safety of PROVENGE.

Adverse Reactions: The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache.

On March 12, 2020 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported the pricing of an underwritten public offering of 8,333,334 ordinary shares at a price to the public of $9.00 per share (Press release, Compugen, MAR 12, 2020, View Source [SID1234555454]). The gross proceeds to Compugen from the offering are expected to be approximately $75 million, before deducting underwriting discounts and commissions and other offering expenses payable by Compugen. In addition, Compugen has granted the underwriters a 30-day option to purchase up to an additional 1,250,000 ordinary shares, at the public offering price less underwriting discounts and commissions. The offering is expected to close on or about March 16, 2020, subject to customary closing conditions.

SVB Leerink and Stifel are acting as joint bookrunning managers for the offering. SunTrust Robinson Humphrey is acting as lead manager for the offering and Oppenheimer & Co. is acting as co-manager for the offering.

The securities described above are being offered by Compugen pursuant to a shelf registration statement on Form F-3, including a base prospectus, that was previously filed by Compugen with the Securities and Exchange Commission (the "SEC") and that was declared effective on August 12, 2019. A final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available for free on the SEC’s website located at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at +1(800) 808-7525, ext. 6218, or by email at [email protected], or Stifel, Nicolaus & Company, Incorporated, Attention: Prospectus Department, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at +1(415) 364-2720 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

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