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Exelixis and Adagene Enter into Agreement to Develop Novel Masked Antibody-Drug Conjugate Therapies

Exelixis, Inc. (Nasdaq: EXEL) and Adagene today announced a collaboration and license agreement under which Exelixis will utilize Adagene’s SAFEbody™ technology platform to generate masked versions of monoclonal antibodies from Exelixis’ growing preclinical pipeline for the development of ADCs or other innovative biologics against Exelixis-nominated targets. Under the terms of the agreement, Exelixis will make an upfront payment of $11 million to Adagene and will have the ability to nominate two targets during the collaboration term. Adagene will be eligible for development and commercialization milestones, as well as royalties on net sales of products developed around each of these targets.

“This partnership with Exelixis strengthens our growing roster of collaborations with global biopharmaceutical companies. We are very pleased to collaborate with Exelixis and look forward to the company’s development of ADCs that leverage our SAFEbody technology.”

“SAFEbody provides a solution to on-target off-tumor toxicity, which is a long-lasting challenge associated with many approved antibody therapeutics,” said Peter Luo, Ph.D., Co-founder, Chief Executive Officer, and Chairman of Adagene. “This partnership with Exelixis strengthens our growing roster of collaborations with global biopharmaceutical companies. We are very pleased to collaborate with Exelixis and look forward to the company’s development of ADCs that leverage our SAFEbody technology.”

Biologic therapies, including therapeutic antibodies such as ADCs, are designed to bind to their targets with high efficiency. However, while the targets for biologic cancer therapies are expressed at high levels in cancer cells, many are also expressed at lower levels on healthy cells. Binding of these therapies to healthy cells may lead to unwanted safety or tolerability issues. Adagene’s SAFEbody platform is designed to overcome this challenge by incorporating a masking peptide that covers the binding domain of the biologic therapy. Specific conditions within the tumor environment allow the biologic therapy to preferentially bind to its target in tumor cells. This allows for improved tumor-specific targeting of antibodies while minimizing on-target toxicity in healthy tissues. Adagene’s most advanced SAFEbody candidate has been approved to start a clinical trial in Australia and the United States.

“As we expand our pipeline beyond small molecule therapies, we are committed to developing novel biotherapeutics that are optimized for safety and efficacy,” said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer of Exelixis. “We believe the SAFEbody platform has the potential to significantly improve the safety profile of ADCs, and we will initially focus on incorporating this innovative technology into novel ADCs that also utilize next-generation linkers and payloads. The combination of these cutting-edge technologies is expected to yield ADC product candidates with differentiated target profiles and/or improved therapeutic indices. We are committed to expanding our development pipeline into additional therapeutic classes even as we drive additional momentum toward broadening the label for cabozantinib into additional cancer indications.”

(Source: Business Wire, 2021)

New COVID-19 Monoclonal Antibody Data Could Shift Clinical Practice

New data from phase 3 trials of monoclonal antibodies for patients with recent COVID-19 diagnoses, or at high risk for SARS-CoV-2 infection, could move the needle on clinician acceptance of the treatments, experts say.

Two monoclonal antibody formulations, Eli Lilly’s bamlanivimab and Regeneron’s cocktail of two antibodies, casirivimab and imdevimab, received emergency use authorizations from the US Food and Drug Administration in November to treat mild to moderate COVID-19 in outpatients. But current recommendations from the Infectious Diseases Society of America’s COVID-19 treatment and guideline panel, based on data from a phase 2 trial of bamlanivimab, suggest against the routine use of the drug.

Data from phase 3 trials, for which the companies announced topline results in press releases last week, could result in a revision of the IDSA guidelines when published more formally and the committee convenes on the issue again, said Jason C. Gallagher, PharmD, a clinical professor at Temple University’s School of Pharmacy and a member of the IDSA panel. It already appears to be encouraging clinician acceptance throughout the country, physicians said.

The new data from Regeneron indicate that people who were recently exposed to SARS-CoV-2 and received its monoclonal antibodies had fewer confirmed infections than people in the trial who received placebo. In Lilly’s trial, high-risk patients newly diagnosed with COVID-19 who received a combination of its monoclonal antibodies bamlanivimab and etesevimab had fewer COVID-related hospitalizations and deaths than those who got a placebo.

“It’s validating what already looked to be going that way,” said Gallagher. “It makes sense that if you give someone passive immunity, it’s going to keep them from being admitted.” However, he did not want to speak for the IDSA committee before they meet, and noted it would need more information than was provided in the press releases.

Physicians critiqued the results of phase 2 trials of monoclonal antibodies for the quality of the analysis and limited scope of the research. Those early findings were “inherently fragile,” Gallagher said, but the results of the phase 3 trials, once published, will provide the most reliable information on the drugs to date.

Regeneron’s results came from an exploratory analysis of 409 randomized participants from an ongoing phase 3 trial testing its monoclonal antibodies for the prevention of COVID-19 in people who live with a COVID-19 patient. The company reported a 50% reduction of overall infections in the treatment group compared with placebo. No participants who received the antibody cocktail had symptomatic infections, while eight in the placebo group did.

Lilly’s trial included 1035 newly diagnosed, high-risk COVID-19 patients and found a 70% risk reduction for hospitalizations and deaths for those who received the monoclonal antibodies compared with placebo. Of 10 total patients in the study who died, all had received placebo. 

(Source: Medscape, 2021)

Eli Lilly teams up with pharma rival GSK and partner Vir for COVID-19 antibody test

COVID-19 has been a real leveler in competitor terms; once warring Big Pharmas have joined forces for the greater good on vaccines, both in R&D and more recently on production, and now on treatments.

Today, Lilly penned a deal with GlaxoSmithKline and biotech partner Vir for its emergency-cleared COVID-19 antibody bamlanivimab 700 mg to be tested in a trial with GSK/Vir’s experimental therapy VIR-7831 (aka GSK4182136) 500 mg.

This isn’t however, a combo trial: GSK told Fierce Biotech that the two drugs are being given to patients together in one of the arms, but as 2 separate infusions.

The hope is that in the so-called Blaze-4 trial, which has been expanded to accommodate the second med, will see the two neutralizing antibodies that bind to different epitopes of the SARS-CoV-2 spike protein create better potency and make the virus less likely to evade, especially with new variants.

This is the first time that monoclonal antibodies from separate companies will be brought together in this way.

Bamlanivimab is a neutralizing antibody directed against the spike protein of SARS-CoV-2 designed to block viral attachment and entry into human cells, thus neutralizing the virus. Late last year, it nabbed an FDA emergency authorization in mild to moderate COVID-19 in patients who are at high risk for progressing to severe COVID-19 and/or hospitalization.

It has, like rival Regeneron which has its own cocktail antibody therapy authorized, struggled to get this therapy to patients across the U.S., and with vaccines now coming in full force, its already limited use will likely further diminish. It’s also contending with new viral variants that could also lessen the impact of the antibody.

This is one reason for tapping VIR-7831, which works as a dual-action monoclonal antibody that was “selected for clinical development based on its potential to both block viral entry into healthy cells and clear infected cells, as well as its potential to provide a high barrier to resistance,” Lilly said in a joint statement.

In early preclinical trials, it showed it could bind to an epitope on SARS-CoV-2 shared with SARS-CoV-1, indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop.

If it can work alongside Lilly’s med and work against new variants with all involved, including the federal government, able to help get patients to these infused therapies better, it could help lower deaths and severe disease. The Blaze-4 trial will run to tell us exactly that.

Just this week, Lilly said in a release (and with thin details) that its internal antibody cocktail bamlanivimab-etesevimab slashes deaths and hospitalizations in high-risk patients

“As the virus continues to evolve, we, along with Lilly and GSK, share the view that we should pursue all possibilities to help end the pandemic and maximize the number of lives that can be saved,” said George Scangos, Ph.D., CEO of Fierce 15 winner Vir.

“This trial is a first step to assess whether the administration of VIR-7831, with its high barrier to resistance and potent effector function, alongside bamlanivimab, which has strong outcomes data in early treatment, can provide potential benefits beyond monotherapy.”

(Source: Fierce Biotech, 2021)