Collaboration to advance development of cancer therapies

Cullinan Oncology—a biopharma firm working on developing a pipeline of targeted cancer treatments—has entered into a collaboration agreement with the Icahn School of Medicine at Mount Sinai (Icahn Mount Sinai). The partnership will focus on the development of novel, small-molecule immune modulators.

According to the partners, the multi-year collaboration arrangement will center around the optimization and development of oral protein degraders targeting hematopoietic progenitor kinase 1 (HPK1), a key regulator of immune cell activation and a high-priority target in immune-oncology. Efforts reportedly will target the acceleration of developing novel, best-in-class HPK1 degraders that stimulate robust anti-tumor immunity.

To learn more about the partnership, Outsourcing-Pharma checked in with Leigh Zawel, chief scientific officer of small molecules at Cullinan Oncology.

OSP: Please tell us a little bit about Cullinan Oncology.​

LZ: Cullinan Oncology is a biopharmaceutical company developing a diversified pipeline of targeted therapeutic candidates across multiple modalities in order to bring innovative medicines to cancer patients. Unlike other companies, we combine a unique portfolio model with innovative sourcing techniques and drug development expertise to discover and advance candidates for potentially transformative oncology drugs.

Our focus is on therapies with first-in-class and/or best-in-class potential that activate the immune system or target key oncogenic drivers with the promise of single-agent efficacy.

Within the past month, we have announced a partnership with the Icahn School of Medicine at Mount Sinai (Icahn Mount Sinai) to identify and advance oral protein degraders targeting hematopoietic progenitor kinase 1 (HPK1), a key regulator of immune cell activation and a high-priority target in immune-oncology. We provided a clinical update from our Phase I/IIa clinical trial of CLN-081, our lead candidate in non-small cell lung cancer (NSCLC) patients whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations that have progressed on or after prior therapy which continued to show a high response rate with favorable safety and tolerability profile.

Importantly, CLN-081 was granted Breakthrough Therapy Designation by the FDA highlighting the urgent need for new treatment options with a differentiated therapeutic profile that can significantly impact patients’ lives. 

OSP: How did you come to work with Icahn Mount Sinai? Has the company and school partnered on projects before?​

LZ: This is the first partnership between Cullinan and Icahn Mount Sinai, who is at the forefront of cancer research and patient care. I have been following the research of Steven Burakoff in the field of HPK1 for many years and have great respect for his contribution and domain expertise.

After delving deep into Jian Jin and Steven Burakoff’s current work on a degrader approach to targeting HPK1, we became confident that such an approach may control tumor growth more effectively compared to simply inhibiting HPK1 kinase activity and can pave the way to a first-in-class and best-in-class therapeutic. We are excited to tie the deep scientific expertise of the Icahn Mount Sinai team to our strong drug development capabilities at Cullinan to advance therapies in this novel area of science.

OSP: Please tell us about this collaboration, including why you’re focusing on HPK1, what each of the parties is bringing to the table, and any details you can offer about what you’re planning, both short- and long-term.

LZ: HPK1 is a high-priority target in cancer because it is a negative regulator of T cell function.  The collaboration aims to accelerate the development of novel, best-in-class HPK1 degraders that stimulate robust anti-tumor immunity. The research will be conducted by leading scientists at both Cullinan and Icahn Mount Sinai. Cullinan will fund the collaboration and has an exclusive option to license the intellectual property for further development and commercialization. We believe this collaboration will help us identify novel, differentiated oral HPK1 degraders with best-in-class potential and can bring benefits to a broad spectrum of cancer patients worldwide.

OSP: Could you please talk about the value of collaboration on drug discovery and development in general? Are there any other collaborations you’ve been involved in or are currently involved in?​

LZ: At Cullinan, we firmly believe that research conducted at or in collaboration with academic institutions and investigators is often the source and inspiration for scientific and medical innovation. Given the complementary expertise, capabilities, and resources, we view an early and flexible academic collaboration framework tailored to the science and infrastructure needs of each project as key in driving efficient drug discovery and development.

The creative funding, licensing, and collaboration structure between Cullinan and Icahn Mount Sinai is a testament to our philosophy in building strong academic partnerships. Our current academic collaborators also include MIT, with whom we are developing a potentially first-in-class and best-in-class IL-2/IL-12 dual cytokine therapy with enhanced tumor retention and tumor microenvironment immune activation compared to existing approaches. We see academic partnering as one of the main drivers for a sustainable pipeline of innovative technology and medicine at Cullinan.

OSP: Is there anything else you would like to add?​

LZ: There are more ground-breaking discoveries and innovations in cancer research today than ever before. At Cullinan, we are committed to leveraging our infrastructure and resources to cultivate, including in partnership with academic collaborators, an ecosystem that efficiently aggregates and develops innovative ideas and discoveries into life-saving medicines.

We put particular emphasis on leveraging novel technologies and biological insights, originating both from within our Cullinan team and from our partners, as the basis for our competitive advantage. We are also creative and flexible in building the economic framework with our collaborators to ensure optimal incentive mechanisms and alignment of interests so that ultimately such innovations have a better chance of improving the lives of patients with cancer.