TumorEnd, LLC, 2013
CM101 – Tumor Destruction via Vascular Disruption
Summary & Phase II Clinical Plans
Researching newborn mortality due to lung capillary attack by Group B Streptococcus, scientists at Vanderbilt University discovered the etiologic agent, a complex carbohydrate metabolite (later termed CM101). Subsequently, in vivo and in vitro, CM101 demonstrated strong potential for destroying tumor vascularity, hypoxically driven, similar to newborn lung capillary development, without disturbing non-tumor vascularity. Specifically, introducing CM101 into the blood stream causes an immunological cascade that targets the body’s immune system to attack tumor vascularity, like the newborn lung, with great specificity.
Importantly, this is distinguished from anti-angiogenesis – which inhibits biological conditions towards generation of new blood supplies. CM101 induces immune destruction of tumor capillaries, as a vascular disruptor, not an inhibitor of angiogenesis.
A Phase I trial on 15 patients (solid tumor cancers) showed 33% of the patients had significant improvement (including one complete cure and another patient with 4+ year life extension). These results are even more remarkable because patients had significantly weakened immune systems (as end stage subjects through chemo and radiation treatment). The minor ‘toxicity’ observed in the trial was pain/discomfort in the tumor (which is indication that treatment is working, was observed in all subjects, plus fever and chills, a diagnostic for presence of cancers.). The lead clinician was Dr. David H. Johnson, a former head of ASCO, and results were published in the journal Clinical Cancer Research.
What happened next is a study in bad management, luck, planning. The drug was being developed by a major pharma which merged with another pharma. New management made a shift to narrow R&D focus to small molecules excluding CM101. The rights reverted to Vanderbilt. As our team at TumorEnd had strong knowledge of the history and potential, when the opportunity recently arose to acquire the rights to advance CM101.
Current Status & Recent Developments
CM-101 offers the opportunity for significant reduction in tumor burden, and possible cure, for patients with immunological competence. Mechanism of action of CM-101 provides opportunities for optimal clinical responses in patients with agressively metastatic tumors having extensive neovascularization.The clinical strategy and first possible oncology indications are numerous and open for active discussion.
The only clinical question for market opportunity rests not on whether such an opportunity exists, but the size of that market and how long and expensive its achievement will be under proper management. Patent protection and FDA extensions provides exclusivity through 2028-2031. Provisions in the Affordable Health Care Act provide exclusivity for biologics 12 years after FDA approval.
Progress on the path to NDA/NBA filing and FDA approval include:
a) Phase I dose-ranging studies in over 24 patients and preliminary acute dose and multiple dose toxicity studies;
b) CMC (chemistry, manufacturing, controls) section components required for the NDA/NBA;
c) pilot manufacturing of three lots; d) cGMP manufacturing of clinical trials materials;
e) initial toxicology and pharmacology preclincal studies in 2 rodent and one non-rodent species;
f) filing IND 4578 (to be re-opened, or re-filed) with the U.S. Food and Drug Administration (FDA).
Prior manufacturing operations were shut down,and replacement capability has been negotiated at a contract manufacturing organization with a proven background in GMP production of bulk drugs for human and veterinary use. The existent CMC section, and prior manufacturing batch records, provide basis for facile technology transfer to the CMO.
Thus, we view the next steps as:
• Re-instituting manufacturing capacity within the framework of the existing CMC section;
• Re-opening/re-filing an IND with the U.S. Food and Drug Administration;
• Establishing clinical regulatory strategy including to identifying the most susceptible tumor subtype, patient population(s), orphan drug opportunities and most expeditious cost-effective route to NDA/NBA;
• Completing follow-on toxicology, immunology, metabolism and biodistribution animal studies as necessary.
• Update the IND file for eventual approval as a biological product.
When these studies are completed, which could be accomplished in less than two years with a total budget on the order of $5M, the product would be poised for a Phase III study leading to fast track and expedited review and approval in the ensuing two years at a cost of less than $10M. Note that a significant portion of this funding maybe available via grants and other government funding.
a) A clinical trial plan executed at Texas Southwestern Medical School Cancer Center under Dr. David Gerber, who has identified funds within Texas to conduct the planned Phase Ic/II trial. TumorEnd would need at least $2M to conduct such a study, therefore the value of this opportunity is clear. The trial is ready to present to the FDA to reopen the existing IND 4578 under which Phase Ia,b successful trials were conducted and published. Dr. Gerber’s department head at Texas Southwestern is Dr. David Johnson, who was the lead oncologist on the Phase Ia,b trials, and remains enthusiastic. The trial is ready to go after manufacture.
b) A quote for cGMP manufacture of sufficient CM101 to conduct the above trial from Benchmark Biosystems in Lincoln, Nebraska. TumorEnd is seeking $1.5M to conduct this manufacture, obtain FDA approvals and transfer the finished drug to Southwestern, including payments to expert consultants.
c) Stage of development of CM101: ready to enter Phase II trials with a record of 33% effectivity in the Phase I. With a pre-money valuation of 8.5M, Tumorend is seeking a 1.5M Preferred Stock investment.
d) TumorEnd has successfully obtained 2 SBIR grants in the past year, therefore validation of our technology has been recently renewed. Under one of these programs we are working on definition of the pharmacophore for CM101, which would constitute completely new composition of matter patenting for CM101, providing a pipeline of future drug development from the pharmacophore.
e) The TumorEnd team includes two of the top world experts in the field of glycomics (with particular expertise in applying glycomics in the realm of cancer).