IGM and ADC collaborate for treatment of patients with non-Hodgkin’s lymphoma
To evaluate imvotamab in combination with Zynlonta
MOUNTAIN VIEW, Calif., Nov 21: IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing IgM antibodies, and ADC Therapeutics SA (NYSE: ADCT) has announced that they have entered into a clinical trial collaboration and supply agreement to evaluate the combination of imvotamab, IGM’s novel IgM CD20 x CD3 T cell engaging bispecific antibody, and Zynlonta® (loncastuximab tesirinelpyl), ADC Therapeutics’ CD19-directed antibody drug conjugate (ADC), for the treatment of patients with relapsed/refractory (R/R) B cell non-Hodgkin’s lymphoma (NHL).
“Patients with B cell non-Hodgkin’s lymphoma are in need of efficacious and well-tolerated treatments,” said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of IGM Biosciences. “We are excited to enter this collaboration with ADC Therapeutics that aims to provide a novel combination regimen targeting both CD19- and CD20-expressing cells for patients with relapsed/refractory B cell nonHodgkin’s lymphoma. We look forward to working with the team at ADC Therapeutics and initiating clinical testing in the first quarter of 2023.”
In data previously reported at the 2021 American Society of Hematology (ASH) Annual Meeting, imvotamab showed a 50% complete response (CR) rate at the likely optimal 100 mg dose (n=10). Of the 28 patients treated in the titration dosing cohorts at that time, cytokine release syndrome was seen in 20% of patients.
“We are pleased to collaborate with IGM Biosciences to explore Zynlonta in combination with imvotamab,” said Joseph Camardo, M.D., Chief Medical Officer of ADC Therapeutics. “This collaboration extends ADC Therapeutics’ commitment to maximizing the potential of our CD19-directed ADC for patients with significant unmet medical needs, both as a single agent and in novel combinations with other anti-cancer agents. The safety profile of imvotamab and the activity observed so far in phase 1 are highly promising for future development.”
Under the terms of the agreement, IGM will be responsible for conducting clinical testing to evaluate the safety and efficacy of imvotamab in combination with Zynlonta® for the treatment of patients with R/R NHL. ADC Therapeutics will provide clinical expertise on Zynlonta® as well as drug supply to support the trial. IGM expects to initiate the trial in the first quarter of 2023. The clinical collaboration is based on compelling mechanistic rationale and preclinical data showing strong activity of this approach.
IGM Biosciences is a clinical-stage biotechnology company committed to developing and delivering a new class of medicines to treat patients with cancer, infectious diseases and autoimmune and inflammatory diseases. The Company’s pipeline of clinical and preclinical assets is based on the IgM antibody, which has 10 binding sites compared to conventional IgG antibodies with only 2 binding sites. The Company also has an exclusive worldwide collaboration agreement with Sanofi to create, develop, manufacture, and commercialize IgM antibody agonists against oncology and immunology and inflammation targets.
Research
Imvotamab is a novel IgM-based CD20 x CD3 bispecific antibody T cell engager (TCE) with the therapeutic potential to be a backbone treatment in hematology. Preclinical research demonstrates that imvotamab may have advantages over IgG bispecific antibodies including greater binding power to CD20 expressing cancer cells especially when CD20 expression has been reduced due to prior treatment with anti-CD20 antibodies. It has also been shown to have good target cell killing efficacy combined with a lower cytokine release profile associated with the T cell directed cellular cytotoxicity (TDCC) mechanism. Data generated from Phase 1 clinical trials provide evidence that imvotamab exhibits a favorable safety and tolerability profile with promising activity in refractory or relapsed NHL patients. Imvotamab is currently being studied in two Phase 2 trials to assess the safety and efficacy of two doses 100 mg and 300 mg, in patients with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).
Zynlonta® is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.
The US Food and Drug Administration (FDA) has approved Zynlonta (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from lowgrade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with Zynlonta. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Zynlonta is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.
ADC Therapeutics (NYSE: ADCT) is a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs). The Company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.
ADC Therapeutics’ CD19-directed ADC Zynlonta (loncastuximab tesirine-lpyl) is approved by the FDA for the treatment of relapsed or refractory diffuse large b-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents.
NEW YORK:“Black Panther: Wakanda Forever” extended its box-office reign in its second week of release with $67 million in ticket sales over the weekend, according to studio estimates Sunday, while “She Said,” about the journalistic investigation into
Harvey Weinstein, struggled in wide release.
After its $180 million launch,
Ryan Coogler’s “Black Panther” sequel slid 63% in its second frame. On its way to more than $1.3 billion in ticket sales, the original “Black Panther” held unusually well, dipping only 44.7% in its second weekend in 2018. But most recent Marvel releases have seen similar or slightly worse declines. “Thor: Love and Thunder,” “Spider-Man: No Way Home” and “Black Widow” all declined 68% on their second weekend.
“Wakanda Forever,” made in the wake of T’Challa star Chadwick Boseman’s death, stars Letitia Wright, Angela Bassett and
Tenoch Huerta. It has amassed $546 million globally thus far, and should continue to drive sales over the upcoming Thanksgiving Day holiday weekend.
The week’s top new release was “The Menu,” the Searchlight Pictures high-cuisine satire starring Anya Taylor-Joy and Ralph Fiennes, who plays a vengeful celebrity chef. “The Menu,” directed by “Succession” veteran
Mark Mylod, grossed $9 million in 3,100 venues. With a 90% fresh rating on Rotten Tomatoes, the well-reviewed R-rated thriller is drawing enough Taylor-Joy fans to outpace most edgier arthouse fare.
Universal’s “She Said” flopped with $2.3 million in 2,022 theaters. The film, starring Carey Mulligan and Zoe Kazan as New York Times reporters Megan Twohey and Jodi Kantor, served as Hollywood’s own big-screen treatment of movie mogul Harvey Weinstein’s downfall. Critics called “She Said,” which premiered at the New York Film Festival in October, a riveting modern-day newspaper thriller, and audiences gave it an “A” CinemaScore. Boxoffice expectations were never particularly high for the $30 million film, directed by Maria Schrader, but it was widely applauded for its tackling of the infamous #MeToo scandal.
Weinstein’s attorneys earlier argued that his Los Angeles trial should have been postponed because of the release of “She Said.” A judge ruled against it. Weinstein is being tried for the alleged rape of two women and sexually assaulting two others. On Thursday, prosecutors rested their case after nearly four weeks of testimony from 44 witnesses.
The weekend’s biggest surprise came from a crowdfunded streaming series about the life of Jesus. The first two episodes of the third season of “The Chosen,” distributed by Fathom Events, collected $8.2 million in 2,009 theaters. Fathom Events is owned by AMC Theatres, Cinemark Theatres, and
Regal Cinemas, and specializes in alternative programming in brief theatrical runs. In “The Chosen,” Fathom found a sizable audience in the religious series. Fathom last year also distributed “Christmas with the Chosen: The Messengers,” which, with $13 million, ranks as the distributor’s biggest hit.
Luca Guadagnino’s “Bones and All,” starring Taylor Russell and Timothée Chalamet as young cannibals, debuted in five theaters before expanding nationwide on Wednesday.
“Bones and All,”is a 2022 coming-of-age romantic horror road film, based on the 2015 novel of the same name by Camille DeAngelis. (AP)