“The power which resides in him is new in nature, and none but he knows what that is which he can do, nor does he know until he has tried,” Ralph Waldo Emerson, Self Reliance
Minerva Biotechnologies’ Core Science: Minerva made a key discovery that will forever change how cancers are treated and prevented. Cancers grow by the exact same mechanism as your earliest embryonic stem cells: the same growth factor receptor, MUC1* (muk 1 star)1, and same growth factor, NME7AB2. But cancer cells just divide, divide, divide, while embryonic stem cells divide, then mature to eventually become a baby. By studying stem cells and cancer cells in parallel, Minerva elucidated the exact genetic changes that induce stem cells to mature and discovered how cancer cells override this natural stem cell shut-off switch to uncontrollably keep dividing until eventually killing the person3. Briefly, cancer cells have turned on a genetic program that brings them back in time to be like your own embryonic stem cells4 that can only divide and cannot function. Like all revolutionary ideas, this one met with skepticism from the scientific community… until we started getting human data in our 1st-in-human clinical trials.
So how do Minerva’s discoveries change how cancers are treated? They eliminate noise in the system. Yes, there are many growth factor receptors and growth factors. Those are the wrong targets. Cancers can, and do, escape treatments by switching to another growth factor or another growth factor receptor. There’s only one growth factor receptor in the early embryo, MUC1*, and only one growth factor, NME7AB. Cancer cells don’t mature, they just go back in time. MUC1* and NME7AB are the ground state.
Minerva developed monoclonal antibodies that bind to the exact site on the MUC1* growth factor receptor that NME7AB binds to. Without NME7AB, MUC1* cannot initiate the signal that results in cell division. One of these antibodies, MNC2, was incorporated into the latest kind of cancer treatment called cancer immunotherapy or CAR T5. Our first clinical trial was huMNC2-CAR44 for metastatic breast cancer patients who had failed up to 14 previous treatments. Most patients responded with tumor shrinkage, no spreading of the cancer or near complete elimination of circulating tumor cells that cause metastasis. Importantly, patients whose tumors expressed a lot of MUC1* outlived their estimated life expectancy by 11.3 months, on average, with no or minimal side effects6. This first CAR T only lives in patients for 3 months. We have now gotten FDA approval for a 2nd CAR T, huMNC2-CAR22, that lives in the patients for years and could actually cure most cancers with a single infusion. We will ask the FDA to allow us to treat any patient with a MUC1* positive cancer, as we have demonstrated complete elimination of breast, lung and pancreatic cancers in animals. We expect to treat the first patient with huMNC2-CAR22 by the end of 2024. Full FDA approval of our MUC1* targeted CAR T could be in Phase 2 with as few as 20 – 30 patients7.
We have also incorporated our lead antibody MNC2 into ADC (Antibody-Drug-Conjugate) format. Unlike CAR T cells, ADCs8 are off-the-shelf drugs that can be repeatedly given to patients for years.
We have also developed monoclonal antibodies against the onco-embryonic growth factor, NME7AB, that activates MUC1*. In animals, these antibodies reverse total metastasis in a few days.
EXIT: Pharma will lose over $236B 2025-2030 when blockbuster drugs go over the patent cliff. Pharma fill their pipelines with patent-protected9 clinical stage assets from small biotech companies, like Minerva. Minerva has built an IP fence around the target, MUC1*, monoclonal antibodies that bind to MUC1*, and those antibodies incorporated into CAR Ts and ADCs.
1 Mahanta 2008 doi: 10.1371/journal.pone.0002054 & Hikita 2008 doi: 10.1371/journal.pone.0003312
2 Carter 2016 doi: 10.1002/stem.2261
3 This simple “cancer switch” mechanism that Bamdad elucidated is based on the same principle that mediates growth vs dormancy in Phage Lambda, a primitive organism; stem cells are our most primitive cell type. Ptashne’s work was the very first discovery of how genes are regulated. A layman’s version of this breakthrough discovery is told in Mark Ptashne’s 1986 book Genetic Switch. Highly cited scientific papers followed, including “Contact with a component of the polymerase II holoenzyme suffices for gene activation,” Cell 1995, of which Dr. Bamdad is an author.
4 Dr. Shinya Yamanaka won the Nobel Prize in Medicine for his discovery of 4 genes that, when expressed in an adult stem cell for 20 days, bring those cells back in time to become the person’s own embryonic stem cell, now called induced pluripotent stem cells. Minerva showed that the Yamanaka core stem cell genes turn on MUC1, NME7AB and the enzyme that cleaves MUC1 to MUC1*, the growth factor receptor form.
5 CAR T: Chimeric Antigen Receptor T cell. Patient’s own immune cells (T cells) are isolated from their blood and engineered to express a kind of phony antibody-receptor. The antibody portion of the CAR directs the CAR T cell to the tumor. Engagement triggers CAR T cells to kill the tumor.
6 By comparison, blockbuster drugs Herceptin and Enhertu were approved based on increased survival of 5- and 6-months respectively.
7 CAR Ts for blood cancers (only 7% of cancers) sold for $12B (Kite) and $9B (Juno). Kite got FDA approval after treating 21 patients in a Phase 2.
8 ADC: Antibody-Drug-Conjugate is an antibody, that binds to something on a cancer cell, chemically coupled to a poison, so is like a directed chemotherapy. Minerva has completed animal studies showing MUC1*-ADCs wipe out breast, lung, pancreatic cancers and others. ADCs are fetching huge valuations - $43B Pfizer acquires SeaGen; $21B Gilead acquires Immunomedics.
9 Minerva’s key patent expiration dates go out to 2036-2044; filed worldwide; represented by Wilson Sonsini Goodrich & Rosati
Contact: Ron Axelrod raxelrod@minervabio.com 617-785-9491; Cynthia Bamdad cbamdad@minervabio.com 617-821-8773
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