In-depth look at innovation on Cancer Research Day
September 24 is World Cancer Research Day, a time for patients, caregivers and companies at the forefront of cancer R&D to look back and look to the future. From cancer immunotherapy to precision medicine and the discovery of new targets and mutations, there is a lot of hope on the horizon, and BioSpace spoke to some of the people leading this groundbreaking research.
Cue Biopharma CEO Dan Passeri is high up in the field of immuno-oncology, calling it “a pretty remarkable field that has emerged”. What started with the work of James Allison, who discovered the immune checkpoint protein CTLA-4, and Tasuku Honjo, who discovered the blocker protein PD-1, has now spawned several companies seeking to take advantage of it.
Cue Biopharma is one such company that tailors an immune response against cancer.
“Our approach is a protein engineering strategy in which we design molecules that are infused into the patient’s body and intended to engage only T cells relevant to cancer,” Passeri explained.
In May, Cue reported that its main active ingredient, CUE-101, has demonstrated a partial response confirmed in a phase I trial in head and neck cancer, a rarity in space.
Passeri is optimistic about the future, saying, “I think this is the most exciting time, where we are starting to really understand how the immune system is regulated, and I think we are actually in a time where l immunology will change. medicine in general.
Based in Belgium, Celyad equips CAR T cell therapies with cytokine interleukin-18 ((IL-18). Clinical biotechnology is developing a diverse portfolio of allogeneic and autologous CAR T cell therapy candidates to attack hematological and solid tumors The allogenic active, CYAD-101, is a CAR T based on the NKG2D receptor currently in phase I of development to treat refractory metastatic colorectal cancer I to treat relapsed or refractory multiple myeloma.
Philadelphia-based Fore Biotherapeutics is offering new hope to patients with untreated cancer mutations by connecting them to hyper-targeted drugs. With its unique functional genomics and machine learning capabilities, Fore tackles tumors caused by rare mutations. The company is examining existing oncogenes to identify mutations classified as being of unknown importance and whether they could be the cause of cancer.
“We go far beyond hotspot mutations and characterize hundreds of new mutations that have not been studied before or are not well understood,” said Fore chief executive officer Usama Malik. “Using the power of our platform, we are able to probabilistically identify which additional mutations may be drivers of cancer and, therefore, where existing therapies or drugs can be applied to patient populations. who do not have existing treatment options. “
Fore’s first program, FORE-8394, is a novel, selective small molecule inhibitor of mutated BRAF. As this program tackles tumor-agnostic indications in fusion, Malik noted, “We know we have very strong activity against CNS tumors, especially gliomas, which have multiple mutations on them.”
Malik told BioSpace that Fore plans to strike another deal in the coming months to have three to four clinical-stage assets by the end of 2022.
X4 Pharmaceuticals of Boston also has an eye on rare cancers, particularly those involving alteration of the CXCR4 pathway, a key modulator of healthy immune cell trafficking and immunosurveillance. The main oncology target of X4 is genetically-derived Waldenstrom’s macroglobulinemia (WM), a slowly growing cancer of the lymphatic system. In June, X4 present positive data from an ongoing Phase Ib trial of the lead drug candidate mavorixafor, a CXCR4 pathway antagonist, in WM, showing significant decreases in serum IgM at low and medium doses. Significant increases in hemoglobin levels have indicated a reduction in bone marrow cancer.
Elicio Therapeutics focuses on lymph nodes, i.e. targeting them to treat aggressive cancers. With its new amphiphilic technology, Cambridge, Massachusetts-based biotechnology delivers potent vaccines and immunotherapeutics directly to the “brain center” of the immune system.
“Lymph nodes are a special site in the body where the immune response comes together,” said Elicio vice president of research Dr. Pete DeMuth. “So many of the cells in our body that are responsible for coordinating immune responses are present in the lymph nodes. “
Elicio’s raison d’être is to enhance the work that has been done so far in the field of immunotherapy with its own unique pipeline of new drug candidates, including those targeting hematologic and cancer-induced cancers. KRAS.
Paris-based OSE Immunotherapeutics is developing a series of bispecific antibody therapies – or antibodies with two targets, PD-1 and anti-interleukin-7 (IL-7), as opposed to one – to enhance the anti-cancer effect of popular PD. -1 checkpoint inhibitors such as Merck‘s Keytruda and Bristol Myers Squibb‘s Opdivo. In May, OSE initiated a Phase II study of its most advanced product, Tedopi, with Opdivo for non-small cell lung cancer (NSCLC). On its own, Tedopi has demonstrated positive results, including overall survival (OS) benefits and a good safety profile in patients with NSCLC after failure of immune checkpoint inhibitor therapy versus chemotherapy.
SOTIO Biotech, based in Prague, is more than just a pony. Interleukin-15 (IL-15) has been shown to increase the number of cytotoxic T cells and NK cells, the two most important cells in driving an anti-cancer immune response. SOTIO aims to maximize this potential in the lead candidate SOT101, which has shown robust in vivo preclinical efficacy in long-term survival and tumor regression in various tumor models. This asset is currently being tested in Phase I. With its BOXR cell therapy platform, SOTIO combats the immunosuppressive microenvironment present in solid tumors to enhance the potential of CAR T cell therapy in these cancers.
Hidden in the sunny bay of Biotech, GigaGen takes advantage of its single cell technology, Surge, to capture and recreate complete antibody repertoires to discover new targets and rare new monoclonal antibodies with unique anticancer profiles.
“The method at our disposal allows us to go very far in the discovery of new antibodies,” said GigaGen co-founder and CEO, Dr David S. Johnson. He went on to explain that instead of making hybridomas (a method of making a lot of monoclonal antibodies), “We’re going to basically take all the B cells from the mice, so millions and millions of cells, and then run microfluidics [the study of the behavior of fluids through micro-channels] to identify antibodies which are of interest as a target.
The company’s main program, GIGA-564, is an anti-CTLA-4 antibody that specifically depletes regulatory T cells in the tumor microenvironment, but does not block the binding of CTLA-4 to B7 ligands. This has the potential to provide superior efficacy and reduced toxicity.
So far, Johnson said, the hypothesis has been extremely well supported by preclinical data.
Based in Woburn, Mass., Abpro also harnesses the power of the immune system to fight diseases, including breast and liver cancer. The company is building a pipeline of T cell activators based on a tetravalent bispecific format (TetraBi), which offers significant benefits including increased potency through bivalent binding to tumor cells, increased safety through functionally monovalent binding to the CD3 and enhanced immune effector function via regional engineered Fc.
Nestled in the heart of Genetown, Ikena Oncology takes a focused approach to discover and develop new patient-centered therapies.
“There is still a lot of opportunity to go much further, both in genetics, in terms of mutations, amplifications and other genetic alterations to ultimately improve options for cancer patients. This is where we focus, ”said Mark Manfredi, President and CEO of Ikena.
Ikena’s pipeline includes experimental therapies for genetically defined or biomarker-induced cancers, allowing it to target specific patient populations that it believes are most likely to respond to treatment. The main IK-930 program is under development for Hippo mutated cancers. This pathway is genetically modified in about 10% of all types of cancer, including NSCLC, ovarian cancer, mesothelioma, and some soft tissue sarcomas.
Manfredi said that in targeted medicine the most important decision one can make is “to make sure that whatever you are looking for is a driver in these indications”.
On the left side, Cardiff Oncology is working to decrease the expression of PLK1, a therapeutic target overexpressed in most cancers. Cardiff is advancing a small molecule PLK1 inhibitor called onvansertib to treat cancers in greatest medical need.
While Cardiff CEO Mark Erlander is optimistic about what is currently possible in cancer, he said: “We have a long way to go. I think we are making a lot of progress, but I also think that the mainstay, unfortunately, remains chemotherapy for many indications. What we’ve been trying to do in this area for 40 to 50 years is to go beyond chemotherapy.
Cardiff’s main program is in second-line KRAS-mutated metastatic colorectal cancer (mCRC), where onvansertib is being tested in a phase Ib / II trial in combination with standard chemotherapy regimens FOLFIRI and Avastin (bevacizumab). In colorectal cancer, about 50% of tumors have KRAS mutations.
On September 8, the company announcement new trial data showing that 7 of 19 patients (37%) had a confirmed partial response. In comparison, the response rate is 5-13% for similar patient populations treated only with standard chemotherapy regimens.
Erlander attributes the dramatic impact to the presence of “great synergy”.
“Onvansertib has what we call a synergy with these two chemotherapy agents. In other words, the sum is greater than the parts. Sometimes what happens is you get a lot more for your money than you expected, and that’s called synergy, ”he explained.