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The FDA hasn’t granted approval for an antibody-drug conjugate in over a year — the last was Immunogen’s Elahere for platinum-resistant ovarian cancer in November 2022 — but the industry pipeline is poised for more.
that’s all 80 ADC candidates It is currently in its third stage of development, according to ZS, a healthcare management consulting and technology company.
Not only can ADCs treat a wide range of oncology therapeutic targets, including breast, non-small cell lung, gastric and esophageal cancers, but they can also be a less risky option than other therapies. ZS estimates that ADCs currently in Phase 3 have a 48% chance of “technical and regulatory success,” compared to 41% for “oncology overall.”
This potential for patients and pharmaceutical companies has made ADCs one of the pharmaceutical industry’s hottest therapies, placing the technology at the heart of several major deals in recent years. AbbVie’s $10 billion acquisition of Immunogen Pfizer’s $43 billion Partnering with Siegen.
While ADCs have already established ROI for many pharmaceutical companies (ZS estimates global sales of approved ADCs will reach $7.5 billion in 2022), further improvements are needed. To improve outcomes and overcome lingering clinical challenges such as off-target toxicity, pharmaceutical companies are adjusting their development strategies.
“ADCs have made a big contribution to improving response rates, but we believe there is still room for improvement.”
Jonas Helma Smets
Chief Scientific Officer, Tubris
Some established leaders in the ADC field, such as Daiichi Sankyo, plan to test their drugs in combination with immunotherapy workhorses like Merck & Co.’s Keytruda, while simultaneously working toward approval in earlier care areas.
Other developers are working to improve the technology, refining ADCs’ three basic components: the antibody that grabs onto cancer cells, the cytotoxic agent that acts as the warhead, and the linker molecule. In a market now filled by most of the pharmaceutical giants and a host of brave new companies, these new candidates hold the promise of producing longer-lasting, less toxic treatments.
Here’s how three emerging players in the ADC space are seeking an advantage.
Genmab focuses on new linker technology
Genmab, a longtime antibody specialist, is a natural fit for the ADC field. In 2021, Tivdak, developed with Seegen, won accelerated approval for metastatic cervical cancer, scoring one of the company’s first ADC wins. Completely nod In April, it was announced that data from a phase 3 trial showed a 30% improvement in survival rates compared to chemotherapy.
Genmab has furthered its commitment to ADC development this year, $1.8 billion acquisition The deal combines ProfoundBio’s ADC platform with Genmab’s antibody therapies and “proprietary technology platform.” The merger launches several assets into Genmab’s pipeline, including a Phase 2 ADC called Rina-S.
“We believe we can be a leader in the gynecological cancer field and differentiate ourselves in the marketplace.”
Anthony Mancini
Chief Operating Officer and Executive Vice President, Genmab
Developed for the treatment of ovarian cancer and other FRa-expressing tumors, the company believes its special sauce — novel linker technology — offers a better safety profile than competing products such as Elaher. Warning Frame For a number of eye toxicities, including serious ones.
“[Lina S]is a second-generation ADC with a cleavable hydrophilic linker, which means it doesn’t have the side effect profile of the first ADCs,” said Anthony Mancini, executive vice president and chief operating officer at Genmab. “With Lina S, we’re not seeing any ocular toxicity.”
As Genmab’s ADC portfolio expands — the company has three candidates in clinical stage, including Rina-S — Mancini said Genmab is positioning itself in the women’s oncology health space.
“With Tivdak now on the market for cervical cancer, we are very excited about Rina-S because these are two drugs that fit our target population,” he said. “We believe this will enable us to become a leader in treating gynecologic cancers and differentiate ourselves in the marketplace.”
Sutro Biopharma aims for multiple ADC breakthroughs
Sutro Biopharma’s flagship product, Luberta, could also be a contender in the ovarian cancer space. In particular, the biotech is looking to leverage its ADC in patients with “low-to-intermediate” FRa expression levels. Fast Track Designation The candidate drug, currently in late-stage development for ovarian cancer, is expected to be launched in 2021.
But the company A wide range of possibilities In indications such as non-small cell lung cancer and other solid tumors.
What sets Sutro’s approach apart from others in the field is that other ADCs use “a mixture of different molecules,” said Sutro CEO Bill Newell.
“We pioneered the idea that if we made a homogenous molecule, we could refine it into a drug that would benefit more patients and be less toxic,” he said. “In the ADC field, that wasn’t possible when I started 13 years ago.”
Sutro has not said when it plans to submit Luberta for regulatory approval, but if it does reach the market, it will target the FRα-expressing ovarian cancer patient population, which is “more than double” that of Elahia, Newell said.
While the company is leading the in-house development of Luberta, it also has a number of partnerships with other pipeline candidates, including: The $900 million Ibsen deal In April, the company announced it would develop a preclinical ADC for solid tumors.
The company also Astellas Pharma in 2022 This research, which is developing immune-stimulatory ADCs (iADCs), could be a groundbreaking approach that Dr. Sutro says “delivers two drugs directly to the tumor, aiming not only to kill tumor cells but also to stimulate an immune response locally against specific tumor cells in the patient.”
Tubulis focuses on more durable ADC payloads
Tubulis, a spin-off company from two German academic institutions, is looking at the next generation of payloads.
The company has six assets in preclinical development for solid tumors, “one of the broadest platforms in the field today,” according to chief scientific officer Jonas-Helma Smets.
Tubulis’ platform suite can “unleash new payloads for the development of versatile, customizable ADCs.” The company In a press release.
“The design space given by this technology in terms of drug-to-antibody ratios, different techniques for conjugating the antibodies is enormous, and we also have new techniques for exploring other payloads,” he said.
Investors are warming to the idea. Tubris raises $138.8 million It will support pipeline development and “clinical proof of concept” for two lead drug candidates.
As the company moves forward toward clinical trials, Helma Smets said Tubulis’ technology could reduce the chance of off-target effects by “ensuring that (the drug) doesn’t lose its payload,” while also producing a more durable treatment.
“In preclinical animal models, we’ve demonstrated that the effect lasts for a long period of time in mice with cancer, and that’s what differentiates us,” he said. “The ADC has been effective in improving response rates, but we believe there is still room for improvement. That durable response is what we hope to translate into the clinic.”
