TMi Raising Money to Convert Destructive Macrophage
Shelley Boyd, MD, president and CSO, Translatum Medicus Inc. (TMi), reports the company has started raising capital to initiate preclinical studies – and possibly Phase II clinical trials – of TMI-018, a drug candidate that might convert potentially destructive macrophages. The company is building a case that aggressive M1 macrophages are the cause of retinal damage and geographic atrophy brought on by Dry AMD. Dr. Boyd says animal studies of TM1-018 suggest those destructive macrophages can be reverted to “neutral” M2 macrophages that perform more of a housekeeping role within the eye. She says TMI has developed an animal model to test TMI-018 as a means of reducing the retinal damage. Dr. Boyd in addition announced the company has expanded its management team and scientific advisory board. It’s also been selected as a charter member of the JLabs incubator in Toronto. TMI hopes to begin preclinical trials next year.
Presenter:
Shelley Boyd, MD, FRCSC
Shelley Boyd, MD, FRCSC, is an Ophthalmologist specializing in diseases of the retina and founding President & CSO of Translatum Medicus Inc(TMi).
Transcript:
Shelley Boyd, MD: Thank you very much. It’s a pleasure to be here at the first OIS@ASRS. Very exciting. There’s our forward looking statements. So Translatum Medicus Inc. is dedicated to saving sight amongst patients with dry AMD. And as you know, there are no treatments for this disease. And I want to remind everyone in the room that 100% of patients with AMD actually have dry disease. Whether it’s early with drusen or pseudodrusen, or late with patches of geographic atrophy, wet neovascularization can occur on top of this. So TMI specifically looked at two challenges that we sort of tried to address, and the first is that the innate immune system is complex. And to date we have not had a phase 3 trial of complement inhibition achieve its primary endpoint. We focus on macrophages, which is the cellular arm. And macrophages are the longest lived cells of the innate immune system, and their behavior profoundly influences the inflammatory milieu. And a resting or M2 M naught macrophage performs a housekeeping function, whereas an inflammatory macrophage is very phagocytic and will destroy incoming pathogens and tissue. TMI also distinguishes itself by having an animal model that actually develops geographic atrophy. And right now we know that reading the eye chart is not a good way to set up a clinical trial. Instead, we focus on measuring those areas. And if you can slow the rate of patch expansion, that is an acceptable endpoint on the regulatory pathway. So TMI’s scientific hypothesis is that those aggressive M1 macrophages are actually responsible for the tissue loss of geographic atrophy. So instead of chewing up pathogens or damaged cells, they actually chew up good retina. Our scientific therapeutic approach would therefore be to convert an M1 back to a neutral macrophage. And that’s exactly what our lead candidate does. And so if you look at those three sort of cartoons there, the lowest one shows messenger RNA production during non-inflammatory conditions of the genes of the M1 complex, or transcriptome. During inflammation, there’s tremendous upregulation of messenger RNA expression, particularly from the MCP1 to 3 gene complex. And TMI-18 is a first in class transcriptional regulator that knocks down that messenger RNA production by altering transcription. So Emmett asked me to focus on what’s new rather than what we’ve done in the past, or what I’ve shown in the past. So I’m going to show you the past in one slide. So we really do focus on translation, that shortest piece of string from unmet need to treatment. So our patients get GA. So first we made a model that actually gets quantifiable GA, and we made that GA expand in our model, and we used clinically relevant equipment. Unlike the clinical setting, though, we can take those animals’ eyes out and what we confirmed is resting macrophages do become M1 during tissue damage. When we put in our drug, we can reduce the size of patch, and we can also prevent, completely prevent patch expansion. This drug – it’s not a drug – lead drug candidate is known to be safe already in phase 2 clinical trials for non-ophthalmic indications, and we’ve patented its use for blinding eye disease. So mechanistically, we can – we’ve confirmed the downregulation of our targets and preservation of the RPE. And we determined this is exquisitely dose sensitive, and if you look at the very right of that graph, this is where we’re completely blocking patch prevention. Looking forward, we’ve actually seen this has – because of the long lifespan of macrophages, this has significant downstream effects. We modulate the inflammasome, and these are 13 of our favorite complement factors. And compared to baseline in our model, we upregulate these and compared to that upregulation when we give our drug, we knock them down. These pieces of data suggest that TMI-18 will be effective on its own and in combination therapy. And we have just confirmed it works in a second animal model. So looking at our whole drug development program, having set up our model and our drug, very excited to announce that we were just selected as charter members of J Labs, the Johnson & Johnson accelerator, and we’ve had additional patents, including international patents, and we’ve been increasing our team. And you know, probably, some of you know me. I’m a retina specialist/ophthalmologist, and I worked at Novartis for the early in-licensing and due diligence around ranibizumab. Our business side is greatly grown with Wayne Schnarr and Ken Howling, and I’m very excited to announce that David Boyer and Philip Rosenfeld and Janet [Sunis?] have joined our advisory group along with Barrett Katz and July Levy, and my PhD student graduated last Friday. And so the big excitement in 2016 is that our friends from BTIG, headquartered in the Transamerica Building here in San Francisco are helping us raise money. And that will help us through sort of three major steps: the rest of the preclinical work to get us through US FDA, and then into our phase 1 2A and ultimately, we envision at least two phase 2’s looking at perhaps high risk patient populations for a prevention study as well as an expansion study. Thank you very