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Redx Signs Clinical Trial Collaboration and Supply Agreement with MSD to evaluate RXC004 in combination with KEYTRUDA® (pembrolizumab) in PORCUPINE2 Study in Biliary Cancer

On December 16, 2022 Redx (AIM:REDX), the clinical-stage biotechnology company focused on discovering and developing novel, small molecule, highly targeted therapeutics for the treatment of cancer and fibrotic disease, reported that the Company has entered into a clinical trial collaboration and supply agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA), for the supply of KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, to be used in the combination arm of Redx’s ongoing PORCUPINE2 Phase 2 clinical study evaluating RXC004 as a potential treatment for patients with biliary cancer (Press release, Redx Pharma, DEC 16, 2022, View Source [SID1234625359]). RXC004, Redx’s lead oncology asset, is being developed as a targeted treatment for Wnt-ligand dependent tumours. It is a potent, selective, oral, small-molecule inhibitor of the Porcupine enzyme, a key activator of Wntligands in the Wnt signalling pathway.

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RXC004 is being investigated both as a monotherapy treatment and in combination, where RXC004 will be combined with immune checkpoint inhibitors (ICIs).

Biliary cancer is known to be heavily reliant upon Wnt signalling, with over 70% [1] of biliary cancer patients showing high Wnt-ligand expression, potentially making this indication highly sensitive to the benefits of Porcupine inhibition. Tumour-derived Wnt-ligand signalling is implicated in reduced intrinsic and adaptive resistance to ICI therapy in multiple cancers [2][3][4]. Inhibition of Wnt-ligand signalling can enhance ICI efficacy by reversing dendritic cell tolerisation, decreasing Treg cells, and reducing the recruitment of myeloid-derived suppressor cells [5]. It has been shown that RXC004 can reverse immune evasion in mouse tumour models and therefore there may be an additive benefit when given in combination with ICI therapies[6] such as pembrolizumab.

Professor Juan Valle, Professor and Honorary Consultant in Medical Oncology, University of Manchester & The Christie NHS Foundation Trust and RXC004 PORCUPINE2 Chief Investigator commented: "Currently, advanced biliary cancer has only a 2% 5-year survival rate, with a critical unmet need for additional treatment options. It is important to study agents such as the Porcupine inhibitor RXC004, which may sensitise some types of tumours to ICI therapies, in an effort to find effective treatment combinations that may improve outcomes for these patients, who have a particularly poor prognosis.

" Dr Jane Robertson, Chief Medical Officer, Redx Pharma commented: "We are delighted to enter into a collaboration agreement with MSD for our ongoing PORCUPINE2 study to evaluate RXC004 in combination with their anti-PD-1 therapy, pembrolizumab. Biliary cancer is a devastating disease that is heavily reliant on Wnt signalling, so we are keen to explore the potential of combining RXC004 with ICIs. Our hypothesis, based on the preclinical data we have generated, is that when combined, there may be a greater chance of the patients showing an immune response, which we hope will lead to improved outcomes.

" About the RXC004 Phase 2 Clinical Trial Programme RXC004 entered Phase 2 clinical trials in November 2021. The first study in the Phase 2 programme, PORCUPINE, (clinicaltrials.gov NCT04907539) is focused on patients with advanced microsatellite stable metastatic colorectal cancer (MSS mCRC) who have progressed following treatment with standard of care and is evaluating preliminary efficacy and safety of RXC004 in genetically selected 16/12/2022, 09:28 View Source

com/public/redx/news/rns/story/rm3jnvx View Sourcecom/public/redx/news/rns/story/rm3jnvx 2/3 patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, advanced MSS mCRC. A second Phase 2 study of RXC004, PORCUPINE2, (clinicaltrials.gov NCT04907851), as a monotherapy for genetically selected pancreatic cancer and biliary cancer, a highly Wnt-ligand dependent cancer, commenced in January 2022.

Given the dual mechanism of action of RXC004, which preclinically was shown to inhibit tumour growth and immune evasion, there is a strong rationale for immune therapy combination. In November 2022, Phase 1 clinical data evaluating the safety and tolerability of RXC004 in combination with nivolumab, in patients with advanced malignancies was presented as a poster at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference. The data was suggestive of an anti-tumour immune response, which is reported to correlate with an improved response to PD-1 immune checkpoint inhibitors. The results of the study supported a dose selection of 1.5mg once daily to be used in combination modules of both PORCUPINE and PORCUPINE2.

The combination module of the PORCUPINE trial will evaluate RXC004 in combination with nivolumab, (OPDIVO-Bristol Myers Squibb, a PD-1 inhibitor) and this module is now approved by the FDA, which will allow patient recruitment to commence in US trial centres. The second module of the PORCUPINE2 study, (clinicaltrials.gov NCT04907851), will evaluate RXC004 in combination with pembrolizumab (KEYTRUDA-MSD’s anti-PD-1 therapy) in biliary cancer. Redx expects to report topline data readouts from the Phase 2 programme starting in the first half of 2023.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.

IMV Announces US$9 Million Registered Direct Offering Priced At-The-Market Under Nasdaq Rules

On December 16, 2022 IMV Inc. ("IMV" or the "Company") (NASDAQ: IMV; TSX: IMV), a clinical-stage biopharmaceutical company advancing a portfolio of therapies based on the Company’s immune-educating platform, DPX, to potentially treat solid and hematologic cancers, reported that it has entered into definitive agreements for the sale of an aggregate of 3,448,276 common shares (or common share equivalents) (each, a "Share" and, collectively, the "Shares") and warrants to purchase up to an aggregate of 3,448,276 common shares (each, a "Warrant" and, collectively, the "Warrants") at a purchase price of US$2.61 per common share (or common share equivalent) and accompanying Warrant in a registered direct offering (the "Offering") priced at-the-market under the Nasdaq Capital Market (the "Nasdaq") rules (Press release, IMV, DEC 16, 2022, View Source [SID1234625354]). The Warrants have an exercise price of US$2.50 per share, are exercisable immediately, and will expire five years following their date of issuance.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the Offering.

The gross proceeds from the Offering to IMV, before deducting placement agent commissions and other offering expenses and excluding any proceeds that may be received upon exercise of the Warrants, are expected to be approximately US$9 million. IMV intends to use the net proceeds from the Offering to continue the clinical development of its lead product candidate, maveropepimut-S, in diffuse large B cell lymphoma (DLBCL), ovarian cancer, the completion of its ongoing basket trial and to continue the development of its proprietary drug delivery platform (DPX) and for general corporate purposes. The Offering is expected to close on or about December 20, 2022, subject to the satisfaction of customary closing conditions.

The Offering will be made pursuant to a registration statement on Form F-10 (File No. 333-266082), effective upon filing with the United States Securities and Exchange Commission (the "SEC") on July 25, 2022 (the "Registration Statement"), and the Company’s Canadian short form base shelf prospectus (the "Base Shelf Prospectus") dated July 22, 2022. IMV will offer and sell the securities in the United States only. No securities will be offered or sold to Canadian purchasers.

A prospectus supplement and accompanying Base Shelf Prospectus relating to the Offering and describing the terms thereof will be filed with the applicable securities commissions in Canada and with the SEC in the United States and will be available for free by visiting the Company’s profiles on the SEDAR website maintained by the Canadian Securities Administrators at www.sedar.com or the SEC’s website at www.sec.gov, as applicable. Electronic copies of the prospectus supplement and accompanying Base Shelf Prospectus may be obtained, when available, upon request by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, or by calling (212) 856-5711 or by emailing [email protected].

For the purpose of Toronto Stock Exchange ("TSX") approval, the Company intends to rely on the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible interlisted issuers on a recognized exchange, such as NASDAQ, provided that the transaction is being completed in compliance with the requirements of such other recognized exchange

Lyell Immunopharma Appoints Lynn Seely, MD as President and Chief Executive Officer

On December 15, 2022 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage T-cell reprogramming company dedicated to developing curative cell therapies for patients with solid tumors, reported that Lynn Seely, MD, a member of the company’s board and former president and chief executive officer (CEO) of Myovant Sciences, has been named Lyell’s president & CEO effective today (Press release, Lyell Immunopharma, DEC 16, 2022, View Source [SID1234625355]). Dr. Seely succeeds Ms. Liz Homans following a four-year tenure as president and then CEO. Ms. Homans will remain a consultant to the company through June 2024.

Dr. Seely has extensive biopharmaceutical leadership experience with a track record of success building companies and developing new medicines in oncology and women’s health. She was previously the president & CEO of Myovant Sciences which gained marketing approval and launched ORGOVYX for men with advanced prostate cancer and MYFEMBREE for women with uterine fibroids and endometriosis. She was previously the chief medical officer at Medivation for a decade where she oversaw the development and marketing approval of XTANDI for men with castration-resistant prostate cancer. She joined the Lyell Board in May 2021 and serves as the lead independent director for Blueprint Medicines. Dr. Seely trained in internal medicine at Yale-New Haven Hospital, completed a basic science and clinical fellowship in endocrinology and metabolism at the University of California, San Diego where she was on faculty before joining industry.

"My decision to transition from my role at Lyell was a difficult one, but I am excited about the next chapter for the company under Lynn’s leadership," said Ms. Homans. "Leading Lyell to become a fully integrated company with two clinical stage programs has been a privilege. I am incredibly proud of the team we have built and all that we have accomplished together. Lynn’s expertise in leading teams to success on complex rapidly moving programs is a perfect fit for this stage of Lyell’s growth."

"Liz has made tremendous contributions to Lyell, building a strong foundation for the company and setting Lyell on a trajectory for success. We support Liz in her decision and thank her for her steadfast leadership," said Rick Klausner, MD, chair of Lyell Board of Directors. "Lynn is a proven leader with deep industry expertise and a history of successfully leading oncology clinical development programs. She has made significant contributions as a board member, and we are delighted she has enthusiastically agreed to step into this leadership position."

"I am honored to be taking on this new role at such an exciting time," commented Lynn Seely, MD, Lyell’s president and chief executive officer. "Since becoming a member of Lyell’s board, I have been so impressed with Lyell’s groundbreaking science, state-of-the-art manufacturing capabilities, and the passion and commitment of the Lyell team to make a transformative difference in the lives of patients with solid tumors. I look forward to working even more closely with our exceptional team to turn Lyell’s vision into reality."

Ferring Receives Approval from U.S. FDA for Adstiladrin for High-Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

On December 16, 2022 Ferring Pharmaceuticals reproted that the U.S. Food and Drug Administration (FDA) approved Adstiladrin (nadofaragene firadenovec-vncg), a novel adenovirus vector-based gene therapy, for the treatment of adult patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (Press release, Ferring, DEC 16, 2022, View Source [SID1234625353]).

"Patients with BCG-unresponsive NMIBC have historically had limited treatment options other than bladder removal surgery," said Steven A. Boorjian, M.D., Carl Rosen Professor and Chair of the Department of Urology at Mayo Clinic, and lead investigator on the recent clinical trial of Adstiladrin. "The approval of Adstiladrin is therefore a significant advance in the current treatment landscape and provides a novel treatment option for patients."

Bladder cancer is the sixth most common cancer in the U.S., with NMIBC representing approximately 75% of all new bladder cancer cases.1,2 BCG remains the first-line standard of care for people living with high-grade NMIBC. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.3

Adstiladrin, an intravesical therapy administered every three months, targets the patient’s own bladder wall cells to enhance the body’s natural defenses to fight cancer. The FDA approval was based on results of the Phase 3 clinical trial, which met its primary endpoint with more than half (51%, n=50 of 98; 95% CI 41 to 61) of patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1) achieving a complete response (CR) by three months. Of the patients who achieved an initial CR, 46% (n=23 of 50) continued to remain free of high-grade recurrence at 12 months.

"The approval of Adstiladrin showcases the power of private industry-academia partnerships in bringing novel treatments to market," said Colin Dinney, M.D., Chairman, Department of Urology, Division of Surgery, University of Texas MD Anderson Cancer Center. "The Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC) defined the clinical trial design required to address this patient population and has been a proud collaborator in the research of Adstiladrin, and we are delighted that such a transformative treatment is now approved by the FDA."

"Ferring has been working diligently to realize the potential of gene therapy for bladder cancer patients, where there has long been a critical unmet need for additional treatment options," said Armin Metzger, Executive Vice President and Chief Science Officer, Ferring Pharmaceuticals. "We are proud to have achieved this critical milestone towards fulfilling the potential of Adstiladrin, a first-of-its-kind therapy, for bladder cancer patients. Adstiladrin is the culmination of a complex research, development, and production process, and we are grateful to the teams, physicians and patients who have helped us reach this approval."

Ferring expects that Adstiladrin will be commercially available in the United States in the second half of 2023, following manufacturing capacity expansion which will see the company pioneering commercial scale vector production for oncology.

For full prescribing information, please visit: View Source

About ADSTILADRIN
Adstiladrin (nadofaragene firadenovec-vncg) is a gene therapy developed as a treatment for adult patients with BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene to do its work. The internal gene/DNA machinery of the cells "picks up" the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into interferon microfactories, enhancing the body’s natural defenses against the cancer. Nadofaragene firadenovec-vncg has been studied in a clinical trial program that includes 221 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849)6.

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.3 Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 20224, 75% of which present as NMIBC.2 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.3 Current treatment options for BCG-unresponsive patients are very limited, and often result in a highly invasive life-changing procedure of radical cystectomy (complete removal of the bladder).5

About the Phase 3 Study
The Phase 3 study of nadofaragene firadenovec-vncg in 157 patients from 33 U.S. sites met its primary endpoint with more than half (51%) of the 98 patients (95% CI 41 to 61) with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1) achieving a complete response (CR), all by three months. Of the patients who achieved an initial CR, 46% (n=23 of 50) continued to remain free of high-grade recurrence at 12 months. In the study, nadofaragene firadenovec-vncg was administered directly into the patient’s bladder by instillation once every three months by a healthcare professional.

The most common adverse events (AEs) observed in the study that occurred in patients in order of decreasing frequency were: instillation site discharge (33%), fatigue (24%), bladder spasm (20%), micturition urgency (19%), and hematuria (17%). The discontinuation rate due to AEs was 1.9%.

The long-term follow-up phase of the four-year study is ongoing, and patients are continuing to be monitored for a total of five years.

IMPORTANT SAFETY INFORMATION
Administer ADSTILADRIN by intravesical instillation only.
ADSTILADRIN is not for intravenous use, topical use, or oral administration.
CONTRAINDICATIONS

ADSTILADRIN is contraindicated in patients with hypersensitivity to interferon alfa or any component of the product.

WARNINGS AND PRECAUTIONS

Delaying cystectomy could lead to the development of metastatic bladder cancer, which can be lethal.
Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.
ADVERSE REACTIONS

The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased (38%), instillation site discharge (33%), triglycerides increased (30%), fatigue (24%), bladder spasm (20%), micturition (urination urgency) (19%), creatinine increased (17%), hematuria (blood in urine) (17%), phosphate decreased (16%), chills (16%), pyrexia (fever) (15%), and dysuria (painful urination) (16%).

To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals at 1 888 337-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

Immunocompromise/immunodeficiency: Avoid in patients with immunocompromise or immunodeficiency.

Evotec achieves further progress in neuroscience collaboration with Bristol Myers Squibb

On December 16, 2022 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) reported that the Company has achieved further significant progress within its neuroscience collaboration with Bristol Myers Squibb (NYSE:BMY) (Press release, Evotec, DEC 16, 2022, View Source [SID1234625352]). The collaboration expands the portfolio by two additional drug discovery projects and has designated a target-based programme for further development, triggering payments in total of US$ 26 m to Evotec.

The collaboration was initiated in December 2016 with the goal of identifying disease-modifying treatments for a broad range of neurodegenerative diseases. Currently approved drugs only offer short-term management of the patients’ symptoms and there is a huge unmet medical need for treatments that slow down or reverse disease progression. The collaboration leverages Evotec’s precision medicine technologies for modality-agnostic drug discovery and development. A first programme originating from the collaboration, EVT8683, was in-licensed by Bristol Myers Squibb in September 2021, following the successful filing of an IND application with the FDA.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, said: "We are delighted to see that after six years our neuroscience collaboration with Bristol Myers Squibb continues to be highly productive across its entire value chain. This is a testament to the scientific excellence and dedication of the teams at Evotec and Bristol Myers Squibb. We are confident that the growing pipeline of promising development candidates will yield transformative therapeutic options for patients living with neurodegenerative conditions."