Merck KGaA, Caris Sign Potential $1.4B Deal to Develop First-in-Class ADCs for Cancer

 Merck KGaA has inked a potential $1.4 billion deal with Texas-based Caris Life Sciences for the discovery and development of first-in-class antibody-drug conjugate candidates for cancer patients, the companies announced Thursday. 

Under the multi-year partnership, Merck KGaA will provide an undisclosed upfront payment to Caris along with research funding. Merck KGaA will also be responsible for the preclinical and clinical research of the discovered targets and the eventual development and commercialization work. 

Caris, an artificial intelligence and precision medicines company, will be eligible to receive discovery, development, regulatory and sales-based milestone payments totaling $1.4 billion and tiered royalties. In return, Merck KGaA secures the exclusive global license to develop, manufacture and eventually commercialize the antibody-drug conjugates (ADCs). 

“This partnership adds to our portfolio of external pipeline programs and is a strong validation of our highly differentiated, orthogonal multi-omics approach to discovering truly novel targets that may be harnessed to eradicate tumors,” Caris Chief Business Officer Brian Lamon said in a statement. 

For the discovery process, Caris plans to combine AI and machine learning along with a patient tissue repository and its research laboratory to find new cancer targets. 

“Through close collaboration with Caris, utilizing their unique discovery platform, we complement our internal ADC capabilities to develop novel first-in-class ADCs and ultimately strengthen our potential to expand our oncology portfolio,” Paul Lyne, the global head of research unit oncology for the healthcare business sector of Merck KGaA, said in a statement. 

Merck KGaA has formed discovery deals in the ADC space before. In 2022, the company paid $30 million upfront, and potentially $800 million in milestone payments, to Mersana Therapeutics to find two new ADC targets. 

Caris has also partnered recently with other companies including a multi-year partnership with Moderna last year to help support the development of its oncology pipeline. In 2023, Caris also established a collaboration with Incyte to help boost precision medicine methods for Incyte’s oncology research.

Merck KGaA’s deal with Caris is the latest in the hot ADC market this week. Genmab announced Wednesday that it will buy the Danish biotech ProfoundBio for $1.8 billion in cash. The acquisition  will give Genmab access to the biotech’s ADC candidates, which are expected to provide Phase I results in 2024 and 2025. 

In related news, French pharma Ipsen added the first ADC to its pipeline on Tuesday via a $900 million deal with Sutro Biopharma, gaining the rights to the preclinical STRO-003 ADC candidate to target solid tumors. 

Market intelligence company Evaluate in a February 2024 report concluded that the ADC market is the “hottest real estate in oncology” and will continue to see investment from large pharma companies reaching a market value of over $30 billion by 2028. 

https://www.biospace.com/article/merck-kgaa-caris-sign-1-4b-deal-to-develop-first-in-class-adcs-for-cancer/

Amylyx to Pull ALS Drug Relyvrio From US, Canada Markets After Phase III Fail

 Amylyx Pharmaceuticals on Thursday announced that it has started the process of pulling its amyotrophic lateral sclerosis drug Relyvrio (sodium phenylbutyrate and taurursodiol) from the U.S. and Canadian markets and will reduce the company’s workforce by approximately 70% under a restructuring plan.

Effective Thursday, Relyvrio will no longer be available for new patients. Those who are currently being treated with Relyvrio can either stay on treatment or transition into a free program, depending on their physician’s advice, according to the company. Amylyx said it will work with the FDA and Health Canada to terminate the marketing authorizations for Relyvrio in these countries.

Joshua Cohen and Justin Klee, co-CEOs of Amylyx, in a statement called the withdrawal of Relyvrio a “difficult moment” for the company and for patients with amyotrophic lateral sclerosis (ALS).

“The decision to remove Relyvrio from the market and provide therapy free of charge for those who wish to continue was informed by the PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community,” Cohen and Keel said.

Last month, Relyvrio failed its highly anticipated Phase III PHOENIX trial, unable to significantly improve scores in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale at 48 weeks versus placebo. Amylyx’s drug also fell short of its secondary endpoints, including slow vital capacity and self-reported health status, as measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire.

Amylyx will present data from PHOENIX at the upcoming American Academy of Neurology meeting, according to Thursday’s announcement. The study’s open-label extension phase is also ongoing, and Amylyx plans to collect survival data from the trial to help inform future studies in ALS.

Losing its only commercial product, Amylyx on Thursday also launched a sweeping restructuring initiative to cut costs and optimize the use of its resources, with an eye toward upcoming clinical milestones. The biotech will lay off around 70% of its employees and lower financial commitments outside of its new priority areas.

Amylyx will now focus on its lead asset AMX0035—which, like Relyvrio, also contains sodium phenylbutyrate and taurursodiol—being developed for Wolfram syndrome and progressive supranuclear palsy. The biotech is also advancing the antisense oligonucleotide candidate AMX0114 in ALS.

CMO Camille Bedrosian revealed in a statement that Amylyx will present Phase II data for AMX0035 in Wolfram syndrome later this month while its Phase III ORION study in progressive supranuclear palsy is set for an interim analysis in mid-2025. The biotech is also preparing to initiate a clinical trial for AMX0114 in the second half of 2024.

The company restructuring and priority changes should extend Amylyx’s cash runway into 2026, according to the announcement.

https://www.biospace.com/article/amylyx-to-pull-als-drug-relyvrio-from-us-canada-markets-after-phase-iii-fail/

eFFECTOR Phase 2 lung cancer trial misses topline threshhold

 eFFECTOR Therapeutics, Inc. (NASDAQ: EFTR), a leader in the development of selective translation regulator inhibitors (STRIs) for the treatment of cancer, today announced topline results from the primary analysis of the randomized Phase 2 KICKSTART trial which tested tomivosertib or placebo, each combined with pembrolizumab, as frontline treatment for patients with non-small cell lung cancer (NSCLC) with PD-L1 ≥50%. Based on 36 events, the hazard ratio for progression free survival (PFS, the primary endpoint of the study) using a stratified Cox proportional hazards model was 0.62 (95% confidence intervals 0.3 to 1.3) in favor of tomivosertib. The two-sided p value for PFS, based on a stratified log rank test, was 0.21, which did not meet the pre-specified threshold of p≤0.2. The median PFS was 13.0 weeks in the tomivosertib plus pembrolizumab arm and 11.7 weeks in the placebo plus pembrolizumab arm, respectively. Overall survival results remain immature, however no trend favoring tomivosertib was observed. There were 67% Grade 3 or higher treatment emergent adverse events in the tomivosertib plus pembrolizumab arm versus 37% in the placebo plus pembrolizumab arm.

https://www.globenewswire.com/news-release/2024/04/04/2857770/0/en/eFFECTOR-Therapeutics-Announces-Topline-Results-of-Phase-2-KICKSTART-Trial-of-Tomivosertib-Combined-with-Pembrolizumab-in-Non-Small-Cell-Lung-Cancer.html

Allurion Expands Virtual Care Suite to US

 Virtual Care Suite (VCS) is now available to license in the United States for providers offering GLP-1 and other anti-obesity medication therapy, bariatric surgery, and weight loss devices

US product launch to kick off at the Obesity Medicine Conference in Denver on April 25

https://www.businesswire.com/news/home/20240404646972/en/

Biotech Eiger Can Take Sentynl's Improved Drug Bid In Ch. 11

 Eiger BioPharmaceuticals Inc. received approval Wednesday to select a $30 million base offer for its Zokinvy drug and use cash collateral after a Texas bankruptcy judge dismissed objections to the relief.

https://www.law360.com/bankruptcy-authority/articles/1820446

TC BioPharma Intends to Acquire NK Platform Technologies

 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, today announced the execution of a non-binding letter of intent as part of its M&A strategy aimed at expanding its therapeutic platform and leveraging NK (natural killer) cells in treating both solid tumors and other indications.

The target asset acquisition covers the proprietary manufacturing process of two allogeneic CAR-NK therapeutics, both of which TCB believes are valuable as monotherapies as well as in conjunction with TCB-008 in the future. Initially, the CAR platforms both are targeted towards solid tumors, including a CD-70 CAR NK technology and an HER2 CAR-NK technology. TCB sees substantial synergies in this potential acquisition, both in clinical therapeutic terms of TCB-008 in combination with the CAR-NK assets, as well as leveraging the existing expertise and human capital of TCB to further advance and refine the manufacturing process while bringing in additional CAR expertise to advance multiple platforms.

Under the terms of the LOI, TC BioPharm has been granted exclusivity while the parties work in good faith on the drafting of a definitive agreement. There can be no assurance that a definitive agreement will be executed or that the proposed transaction will be consummated on the terms or timeframe currently contemplated. TC BioPharm's Board of Directors' approval and disclosed thereafter. Upon execution of the definitive agreements, the completion of the transaction will be subject to, among other matters, satisfaction of the conditions negotiated therein, the Company having secured adequate financing, and receipt of all third party (including governmental) approvals, licenses, consents, and clearances, as and when applicable. There can be no assurance that the Proposed Transaction will be completed on the terms contemplated in the LOI or otherwise.

https://www.prnewswire.com/news-releases/tcbp-announces-execution-of-non-binding-letter-of-intent-for-acquisition-of-nk-platform-technologies-302108362.html

After Brain Cancer Data, Candel Shares Good News From Pancreatic Cancer Study

 Thursday, Candel Therapeutics Inc (NASDAQ:CADL) released updated interim survival data from the ongoing phase 2 trial of CAN-2409 plus valacyclovir (prodrug), together with standard of care (SoC) chemoradiation, followed by resection for borderline resectable pancreatic ductal adenocarcinoma.

Survival data were updated with eight months of further follow-up since the first analysis was presented at the 2023 Society for Immunotherapy Annual Meeting.

Data Highlights as of March 29, 2024, Data Cut-off, Include:

Prolonged and sustained survival was observed after experimental treatment with CAN-2409 in patients with borderline resectable PDAC (n=13).

The estimated median overall survival was 28.8 months in the CAN-2409 group versus only 12.5 months in the control group.

At 24 months, a survival rate of 71.4% was observed in CAN-2409 treated patients after SoC chemoradiation and before surgery, versus only 16.7% in the control group.

At 36 months, a survival rate of 47.6% was estimated in patients who received CAN-2409, together with SoC chemoradiation before surgery, versus only 16.7% in the control group.

4 out of 7 patients who received CAN-2409 were still alive at the time of data cut-off, with two patients surviving more than 50.0 months from enrollment.

Only 1 out of 6 patients, randomized to control SoC chemotherapy, remained alive at data cut-off (alive at 50.6 months).

Previous analysis of blood and resected tumors showed consistent and robust activation of the immune response after experimental treatment with CAN-2409.

In pancreatic tissue of patients treated with CAN-2409 plus prodrug and SoC, dense aggregates of CD8+ granzyme B positive cytotoxic tumor-infiltrating lymphocytes, dendritic cells, and B cells were observed.

CAN-2409 continued to be associated with a favorable safety/tolerability profile.

https://finance.yahoo.com/news/brain-cancer-data-candel-therapeutics-162431850.html