Postcards from the Field
Some green shoots of investing progress as MissionGBM welcomes its 300th case
It is the dog days of summer, but the cases just keep coming. We don’t mind – this is what we do.
Green Shoots
We are beginning to see higher quality programs with improved scientific content. Huzzah! We like to think that the constant messaging that we publish regarding an Investable Profile (see our five part “Investing in Brain Cancer” series) is helping to shift the conversation onto a more actionable footing.
The Highlights:
DNA Damage Response/Repair. We have always been supportive of therapeutic agents that target DNA Damage Response/Repair (“DDR”) mechanisms. Current research has ventured far beyond older agents to emphasize much more brain-penetrant and targeted agents. When combined with complementary medicines like brain-penetrant PARP-1 inhibitors, the story and #Data become quite interesting. There are multiple validated targets available, so careful prioritization based on the full spectrum of #Data will be necessary to optimize progress and prevent premature clinical trials failures for the usual reasons (e.g. no neuropharmacology data; inadequate PK/PD). Even more heartening is the clear increase in activity and interest that we see from organizations across the expanse of brain cancer research and strategic investing ranging from the DNA Damage Response Consortium at NBTS to several Big Pharmas. Confidentiality obligations prevent us from commenting more specifically at this time, but watch this space.
Immunotherapy. We believe that immunotherapy must be a necessary part of a combination regimen in order to significantly alter the treatment prognoses for brain cancer patients. At the moment, we are active with more than a dozen companies and research efforts focused on innovating immunotherapies across the range of modalities – Immuno-Oncology, Cell Therapies (CAR-T, CAR-NK, TCR-T, Gamma-Delta T, Antibody-Targeted T-cells), Tumor-Infiltrating Lymphocytes, Gene Therapies, Vaccines, Oncolytic Viruses and some really “out there” approaches. Given our perspective, we see increasing evidence of the convergence of a handful of mechanistic pathways that these approaches have in common. This is good thing because it signals that cross-pollination of the data sets will allow the field to more rapidly understand those targets and pathways that deserve increased attention and development. It should also make it clear that some approaches are going to struggle to move forward (e.g. low valency CAR-T without TME stimulation and checkpoint inhibition; No, lymphodepletion is not the answer). Confidentiality obligations prevent us from commenting more specifically at this time, but watch this space.
Ancillary Targets and Mechanisms. We have previously written about the attractiveness of certain, well-chosen ancillary (not directly oncogenic) targets and mechanisms to be included in combination treatment protocols (see here). One Seed program in particular is looking rather promising, and has generated a #Data package of sufficient quality to merit exploring a range of strategic investing options. We are directly involved, and believe that this program will yield compelling translational evidence as well as a visible example of a model for investing in brain cancer. Confidentiality obligations prevent us from commenting more specifically at this time, but watch this space.
Certain Device-based Approaches. We continue to think that medical devices will have an important role to play in brain cancer treatment regimens. Of the four opportunities that we advanced in our Brain Cancer group at a major institutional investor, all involved a medical device to either (i) enhance trans-BBB drug delivery; or (ii) affect a biophysical mechanism that could be exploited as part of an overall treatment protocol. The challenge is consistently that device companies do not generally “speak molecular language” or have a staff that has experience with the Research and Regulatory methods and processes that one uses in the Biopharma world*. We have seen several protracted clinical holds imposed on device companies when they have attempted to advance drug-device combination programs into clinical and Regulatory stages because they have not incorporated the necessary pre-clinical studies to generate the required data. This is a solvable problem, and we encourage device companies to seek out expertise in the molecular world as part of their strategic planning.
*We had one Investor/Director of a device company (a computer engineer by background) confidently tell us that the mechanistic rationale for the device was that “cancer cells do not use mitochondria while normal cells do”. You can imagine our reaction.
Expanding Investor Interest. Institutional and Strategic investor interest in brain cancer has been measurably expanding over the last 18 months. There are syndicates forming. We are involved in multiple discussions on a weekly basis with several of them evolving into Seed investments ($2-5M) designed to generate #Data sets that seek to bridge the translational research gap between early stage discoveries and #Data packages that support opening early stage, well-conceived clinical trials. This is real progress because, over time, the investor conversation needs to shift from that of “Uninvestable Space” (historical situation) to “The Data Support It” (based on rigorous science- and evidence-based programs). We are not naïve. The transformation of investor interest in brain cancer will take time and will absolutely be built on high quality science. However, we also are confident that several programs will advance from the Seed stage to the point that typical Series A and B rounds with Tier 1 syndicates will be possible ($40-100M).
It's a Rough Neighborhood
We recently began working with our 300th MissionGBM case. Our motivation for founding MissionGBM in 2022 was to scale the resources (science, clinical, investing) at our disposal to assist other brain cancer patients and families worldwide in a way that we did not see operating in the space. Each case is a personal story, and we get to know the patient and patient’s family as part of the Journey. While we know that we have been able to help many families, no one bats 1.000 in brain cancer. A few patients have lost their fight, and that just makes us want to go even harder at our objectives. On the other hand, we have many cases that are out beyond three years post-diagnosis…and counting…and most of these cases have unfavorable clinical and tumor molecular profiles. The tenacity and never-give-up spirit of some of the families buoys us. We hope to have a few of them join us for a “Community” video chat this year.
We Get By With a Lot of Help from the Team
We owe a debt of gratitude to the MissionGBM Team, a group of individuals hand-selected for their leadership in brain cancer research and clinical practice. The reader can see many of the of these people featured under the “Meet the Team” and “Brain Cancer Science Talk” tabs on the MissionGBM homepage, and we expect that others will be added in the future. Not a single person in the Team believes SoC is an acceptable goal for brain cancer patients. Everyone is open-minded and constantly pushes the envelope to redefine the state-of-the-art. We frequently cross-pollinate ideas, and a few of the Team members are co-authoring grants and investment proposals together. This is how we change the field, and advance it based on a foundation of rigorous science. Moreover, the clinicians on the Team have been beyond generous with their time. They have agreed to see MissionGBM patients without hesitation; have jumped on peer-to-peer consults with fellow clinicians; and have continuously come up with ideas around the clock (they all know that I will likely respond in real time at 2am). Sometimes this means a Zoom call from their car in the parking lot of a child’s lacrosse game (at half time); a quick consult during a break in a daughter’s graduation party; or locating WiFi to send a message while on safari in Africa. Recently, one Neuro-Oncologist at a leading Center commented that the MissionGBM Team is “the best virtual Tumor Board around”. We do what we can.