Enhancing Capabilities: Tahi Ahmadi from Genmab in a Riveting Dialogue Exchange with PharmaShots

Shots:

Recently, Genmab acquired ProfoundBio in a strategic move to strengthen its position in the ADC space. With this acquisition, Genmab gets ProfoundBio’s novel ADC technology platforms

Today, at PharmaShots, we have Tahi Ahmadi, EVP and Chief Medical Officer at Genmab, sharing insights from the recent acquisition of ProfoundBio by Genmab

With this acquisition, Genmab looks forward to advancing next-gen medicines and integrating ADC technology and people powering them into Genmab

Saurabh: Congratulations on the acquisition of ProfoundBio, this looks like a great strategic move to significantly enhance your oncology portfolio and innovative capabilities. Could you tell us more about this strategic move of acquiring ProfoundBio and how this acquisition aligns with Genmab’s long-term goals?

Tahi: The acquisition of ProfoundBio is a strategic move that perfectly aligns with our long-term strategy and propels us toward our 2030 vision to transform patients’ lives with our knock-your-socks-off (KYSO®) antibody medicines. ProfoundBio brings to Genmab novel ADC technology platforms, including a proprietary hydrophilic linker-drug platform that is the basis of rinatabart sesutecan (Rina-S) – an investigational topoisomerase-1 (Topo1) ADC targeting FRα for the treatment of ovarian cancer and other FRα-expressing solid tumors. These platforms complement our existing suite of proprietary next-generation (next-gen) antibody platforms and position us as a potential leader in ADC space. Together, these platforms open exciting new possibilities as we aim to develop more groundbreaking KYSO® medicines.

Saurabh: How do you plan to leverage worldwide rights to three candidates in clinical development, including Rina-S, plus ProfoundBio’s ADC technology platforms?

Tahi: With the acquisition, Genmab has gained worldwide rights to three promising clinical-stage candidates: the previously mentioned Rina-S, along with two clinical programs: PRO1160, an ADC targeting CD70, and PRO1107, an ADC targeting PTK7. A fourth asset just cleared IND, PRO1286, is a novel EGFR- and cMET-dual targeting ADC.

We’re planning to use ProfoundBio’s innovative ADC technology platforms, including the proprietary hydrophilic linker-drug platform as well as proprietary and novel payloads, to enhance our existing capabilities. We will leverage these capabilities to add additional candidates to our pipeline in the near future.

Saurabh: Can you elaborate on Rina-S, its MOA, and the P-I/II results of Rina-S?

Tahi: Rina-S is an investigational ADC comprised of a FRα-directed antibody conjugated to sesutecan, a novel, proprietary hydrophilic exatecan-based linker-drug, LD038, at a homogeneous drug-to-antibody ratio (DAR) of 8. Exatecan is a highly potent, membrane-permeable investigational Topo1 inhibitor with a strong bystander effect that has been studied as a small molecule anticancer agent. Sesutecan is a highly hydrophilic stable, cleavable linker designed to mask the hydrophobicity of conjugated exatecan on the ADC, enabling high DAR and efficient delivery of the exatecan payload to tumors while maintaining favorable physicochemical and pharmacokinetic properties of the ADC.

We believe that Rina-S has the potential to broaden, deepen, and consequently expand activity beyond what has been seen with FRα approaches. In addition, it has shown a potentially differentiated safety profile in clinical development thus far. This potential differentiation is a direct result of the novel proprietary hydrophilic linker technology developed by ProfoundBio. Following the encouraging 2023 SITC Phase 1/2 data, we anticipate additional data sets will be available in the second half of this year.

Saurabh: Apart from Rina-S, what other products from ProfoundBio’s portfolio are you excited about?

Tahi: We’re also excited about two other clinical programs, PRO1160, an ADC targeting CD70, and PRO1107, targeting PTK7. There’s also a pre-clinical, bispecific ADC, PRO1286, targeting EGFR x cMET, two clinically validated, broadly expressed solid tumor antigens. Looking ahead, we’ll carefully evaluate our combined clinical programs and follow the data and the science as we determine the path forward for all our KYSO® programs.

Saurabh: Rina-S has been granted FTD by the US FDA. How does this influence your regulatory strategy and when do you plan to launch the drug in the market?

Tahi: Based on the data we have seen; we are planning for a broad development of Rina-S in ovarian cancer and other folate receptor alpha-expressing solid tumors. We believe that Rina-S is registration-ready, and we intend to expeditiously initiate pivotal registration-enabling trials, including Phase 3 trials. As our plans develop, we will share additional details.

Saurabh: Can you please tell us about the anticipated projects after the integration of Genmab and ProfoundBio?

Tahi: Antibody technology, capabilities, and know-how form the foundation of both Genmab and ProfoundBio, so by bringing our teams together, we will be uniquely positioned to advance next-gen medicines. In the coming months, our priority is to integrate the ADC technology and the people powering them into Genmab. We also look forward to broadening the development plans for Rina-S in ovarian cancer and other FRα-expressing solid tumors. At the same time, we’ll be looking for ways to leverage our combined power and expertise to develop new medicines with the potential to transform the treatment of cancer and improve patients’ lives.

Saurabh: How does ProfoundBio’s ADC technology platform complement Genmab’s existing technology platform?

Tahi: The addition of ProfoundBio deepens our presence in the gynecologic oncology (gyn-onc) space and strengthens our foundation in solid tumors. Given that Rina-S is the second ADC in development in our gyn-onc portfolio, we’ll be able to generate value through our development expertise, while also building upon the commercialization success of our current portfolio. Further, the combination of ProfoundBio’s novel ADC technology with Genmab’s proprietary next-generation antibody technology platforms creates new opportunities in the long term, allowing us to pursue our goal of having a stronger impact on the lives of patients.

Image Source: Canva

About the Author:

Tahi Ahmadi

Dr. Ahmadi joined Genmab in 2017 and became the Executive Vice President and Chief Medical Officer, Head of Experimental Medicines effective March 1, 2021. He holds an M.D. from the University of Cologne (Germany) and a Ph.D. from the University of Freiburg (Germany) and has expertise in translational research, strategic product development, global regulatory submissions and clinical development. Prior to joining Genmab, Dr. Ahmadi was head of experimental medicine and early development oncology at Janssen and a member of the Senior Leadership Team for Oncology.

During his time at Janssen, he led the global development of daratumumab including clinical R&D and medical affairs strategy across indications and was instrumental in the clinical development and initial FDA NDA submission for Ibrutinib. Prior to joining Janssen, Dr. Ahmadi was a faculty member of the Department of Hematology and Oncology at the University of Pennsylvania. Dr. Ahmadi is an author on a number of scientific articles that have been published in journals such as NEJM, Lancet, JCO and Blood, among others.