Opportunity to License/Acquire CMX-2043 For Treatment of Traumatic Brain Injury

Ischemix is a privately-held US company developing a novel cytoprotective drug, CMX-2043, for the treatment of acute moderate-to-severe traumatic brain Injury (TBI), a market for which there are no approved drug treatments and which offers the opportunity for premium pricing of an approved product.

An estimated 2.8 million people go to emergency departments in the US each year due to TBI; many more cases go unreported/unrecorded. Approximately 5 million people are living with TBI disabilities today in the US alone.

CMX-2043 is a pleiotropic (multi-modal) compound with demonstrated efficacy in several different translational studies of traumatic brain injury, including a recent comprehensive porcine TBI study, the preferred animal model.

CMX-2043  has demonstrate excellent safety and tolerability in a Phase 1 SAD/MAD trial.  Ischemix recently received favorable feedback from FDA on the overall CMX-2043 development program as well as the plans for the next Phase 2a proof of concept study in patients with acute severe TBI. The Company believes there is scope for a subsequent potential registrational trial with a Ph2b/3 adaptive design.

In a recently completed study in pigs, the model of choice and highly translatable to humans, CMX-2043 achieved remarkable and significant improvements (p<0.05) in 6 key MRI measures compared to placebo:

•        Brain tissue swelling: @ 24h, ↓ 68-70%, and atrophy @ day 42, ↓ 43-48%

•        Injury lesion volume:  @ 24h, ↓ 45-46%, @ day 7, ↓65-66% and @ day 42, ↓45-46%

•        Hemorrhage volume: @ 24h, ↓ 51-58%, @ day 7, ↓71-76%

•        Cytotoxic edema:       @ 24h, ↓ 30-60%, @ day 7, ↓ 49-71%

•        Cerebral blood flow:   @ 24h, ­ ↑ 46-56%, @ day 7, ­  ↑ 46-57% and @ day 42, ­ ↑ 47-63%

•        WM integrity (FA):     @ 24h, ­  ↑ 66-70%, @ day 7, ­  ↑ 62-70% and @ day 42, ­ ↑ 62-66%

Ischemix knows of no other product that has achieved such results in TBI.

Because the characteristics of a pig brain are very similar to those of humans it is reasonable to expect that these results achieved can also be achieved in humans.

Moreover, the primary driving pathology in most injuries, TBI, cardiac, renal, etc. is ischemia, a reduction in local blood flow or oxygen delivery.  These are all followed by secondary injuries caused by the body’s response – typically inflammation and cellular repair.  This is important because the positive results achieved in previous studies of CMX-2043 in patients with acute cardiac ischemia is direct evidence that CMX-2043 mitigates the pathology of such events and as such should be agnostic to any specific organ tissue.  This further supports the translatability of 2043’s results in pigs to humans.

Ischemix has cost estimates from CROs for a trial of ~ $13million. About 95% of this cost is incurred during the acute period of hospitalization which will be less than 30 days.  The day 30 top line results would be compelling and would be available relatively quickly. Additionally, Ischemix estimates that by the time the last patient completes 30 days, more than 2/3 of the subjects will have completed the follow-up evaluations at 3 to 6 months.

In view of the large unmet need and market potential, this relatively inexpensive, quick and risk-mitigated POC study would appear to be a reasonable investment for a partner. Relatedly, Ischemix has indicated its willingness to have the majority of consideration for a license agreement with a partner paid upon achievement of significant clinical and regulatory objectives.

Because the characteristics of a pig brain are very similar to those of humans it is reasonable to expect that these results achieved can also be achieved in humans.

Moreover, the primary driving pathology in most injuries, TBI, cardiac, renal, etc. is ischemia, a reduction in local blood flow or oxygen delivery.  These are all followed by secondary injuries caused by the body’s response – typically inflammation and cellular repair.  This is important because the positive results achieved in previous studies of CMX-2043 in patients with acute cardiac ischemia is direct evidence that CMX-2043 mitigates the pathology of such events and as such should be agnostic to any specific organ tissue.  This further supports the translatability of 2043’s results in pigs to humans.

Ischemix has cost estimates from CROs for a trial of ~ $13 million. About 95% of this cost is incurred during the acute period of hospitalization which will be less than 30 days.  The day 30 top line results would be compelling and would be available relatively quickly. Additionally, Ischemix estimates that by the time the last patient completes 30 days, more than 2/3 of the subjects will have completed the follow-up evaluations at 3 to 6 months. In view of the large unmet need and market potential, this relatively inexpensive, quick and risk-mitigated POC study would appear to be a reasonable investment for a partner. Relatedly, Ischemix has indicated its willingness to have the majority of consideration for a license agreement with a partner paid upon achievement of significant clinical and regulatory objectives.

CMX-2043 has a composition of matter patent valid to at least 2031 and method of use for TBI until at least 2038. Ischemix believes that there are significant opportunities to create novel formulations of CMX-2043 and has begun development on these to extend patent coverage and to better access different patient populations.

Please contact us to arrange a discussion call about Ischemix and CMX-2043.