CONFIDENTIAL Conference Call Transcript Gemini Therapeutics and Disc Medicine Merger Agreement Announcement

Conference Call Transcript

Gemini Therapeutics and Disc Medicine Merger Agreement Announcement

August 10, 2022 / 08:00 AM ET

CORPORATE PARTICIPANTS

Georges Gemayal Gemini Therapeutics, Chair of the Board and Interim CEO

John Quisel President and CEO of Disc Medicine

Welcome to today s joint call with Gemini Therapeutics and Disc Medicine. Our speakers today are Georges Gemayal, Chair of the Board and Interim CEO of

Gemini Therapeutics, and John Quisel, President and CEO of Disc Medicine.

Georges Gemayal Gemini Therapeutics, Chair of the Board and Interim

Gemini s strategic review was a thorough and thoughtful process. We believe that this transaction presents an exciting opportunity for our

shareholders, as Disc has built a diversified, clinical-stage pipeline of product candidates, and we believe in the ability of Disc s experienced management team to lead the combined company. We look forward to its continued success. John will

now provide an overview of Disc Medicine and the company s hematology drug development programs.

John Quisel President and CEO of Disc

Thank you, Georges, and good morning everyone. Before I begin, I want to remind everyone that this discussion and the accompanying presentation

will contain forward-looking statements based upon the current expectations of Gemini Therapeutics and Disc Medicine, which include, but are not limited to statements regarding the expected timing, completion, effects and potential benefits of the

transaction and our future expectations, plans and prospects for the combined company. Such statements represent management s judgment and intention as of today and involve assumptions, risks and uncertainties. Gemini and Disc undertake no

obligation to update any or revise any forward-looking statements. This slide provides an overview of these forward-looking statements and the risks and uncertainties that could cause actual outcomes and results to differ materially from those

contemplated in these forward-looking statements. Please refer to the accompanying slide for more details on these forward-looking statements.

as indicated on this slide, Gemini intends to file a registration statement and accompanying proxy statement and prospectus with the SEC relating to the proposed merger. Please be advised to read, when available, the proxy statement and prospectus

and other relevant documents filed with the SEC as these will contain important information about Gemini, Disc and the transaction. Once available, these documents can be obtained free of charge from the SEC at sec.gov or on Gemini s

Now with those preliminaries completed, I m delighted that we ll be joining with Gemini through this merger. I will briefly

summarize the components of the reverse merger transaction first and then discuss the business plans here at Disc Medicine.

We believe this merger will be transformative. At Disc we have now become a mid-stage clinical biotech company with

multiple drug development programs focused on hematologic disorders. With two first-in-class molecules in patient trials across three disease areas, we anticipate near

term clinical catalysts in the next 6 to 12 months. The combined financial strength of Gemini and Disc is expected to finance our business plan into 2025 with an expected approximate $175 million cash and cash equivalents at close.

As an overview on the merger terms, upon the closing of the transaction the company will be renamed Disc Medicine and will begin trading on NASDAQ under the

ticker symbol IRON. The ticker symbol is a reference to our therapeutic focus on modulating iron metabolism. After the merger, the currently expected ownership breakdown is projected to be as shown on the slide, and we expect approximately

$92 million raised from Gemini plus an additional $53.5 million from a concurrent financing. There will be a contingent value rights agreement, or CVR, associated with the legacy Gemini programs that are referred to as GEM103 and GEM307,

and any net value received from future transactions for these assets will flow to the pre-existing Gemini shareholders. We expect the merger transaction to close in the fourth quarter of 2022, subject to

approval of shareholders at both companies. The merged company will be managed by the existing Disc Medicine team and board, and we are delighted that Georges Gemayal will be continuing as a director of the combined company

Now I will summarize the Disc Medicine business plan. We have been working for many years to build a great hematology company. We think this is an excellent

therapeutic area for building a company. Unmet patient needs are high and the tools for clinical development include readily measurable and objective endpoints. Our approach focuses on fundamental components of red blood cells, particularly the

metabolism of heme and iron, which are universal and critical components of these cells. There is evidence from studies in humans that both of our clinical-stage molecules engage their respective targets and cause the desired effect on iron

metabolism and heme biosynthesis. There is also strong evidence in human genetics for the importance of our targets in iron metabolism. Because of the universal need for heme and iron in red blood cells, we believe each program has potential to

address a broad range of multiple indications.

I will focus on our two clinical-stage programs. One is called bitopertin which was in-licensed from Roche in 2021 and is now starting a Phase 2 trial in an indication that we refer to in brief as EPP, or erythropoietic protoporphyria. We have also now initiated one of two near term phase 1b/2a

studies for our DISC-0974 antibody program. The first of these, for the treatment of myelofibrosis patients with anemia is now open and enrolling, and later this year we expect to be opening a trial in anemic patients with chronic kidney disease.

This clinical activity puts us in a position to have many potential near-term catalysts. We expect across the next 6-12 month to have readouts on bitopertin in the EPP trials and DISC-0974 in the two trials of

anemia of inflammation in myelofibrosis and chronic kidney disease. As I mentioned, we also believe that both of these drugs have the potential to expand into other indications.

I believe we ve built a fantastic team with strong experience in drug discovery and development. So we are positioned to take our programs deep into

clinical development and potentially transition to a fully integrated biotech company should we be successful.

Our investors are a group of top-tier biotech specialist investors. We were founded and seeded at Atlas Ventures. Novo Holdings led the Series A along with Access Biotechnology and OrbiMed led the Series B along with Arix. They were joined by a

host of other top-flight groups such as Janus Henderson, Rock Springs and 5AM. We also benefit from an experienced Board of Directors and a scientific advisory board representing top names in our field.

What we re doing at Disc is engaging fundamental biology in red blood cells and if you think about it, what is a red blood cell other than a cell

that s full of hemoglobin to carry oxygen. The key components of hemoglobin are iron and heme, so our programs are designed to control the incorporation of iron and heme into newly forming red blood cells, thereby controlling fundamental

aspects of red blood cell biology. We believe that these targets and this approach will allow us to address a wide range of indications, examples of which are listed at the bottom of the slide. You ll hear about three or four of these

indications over the course of this discussion where we have clinical trials either open or in near-term planning, and we expect to be able to access this full range of indications over the lifecycle of these programs.

In terms of our pipeline chart, we have our heme biosynthesis portfolio led by bitopertin, a molecule that, as I said previously, we in-licensed from Roche. This is a small molecule, given orally, once daily. Bitopertin inhibits heme biosynthesis by targeting GlyT1, a glycine transporter expressed on red blood cells. We are now open and enrolling

on a Phase 2 trial in Australia in EPP patients and we expect to be opening a similar trial in the US shortly, referred to as the BEACON and AURORA trials, respectively. We are also in planning for a trial in a rare anemia called Diamond-Blackfan

Anemia, as well as other potential indications.

The founding portfolio of the company was around iron metabolism where there s a central regulator

called hepcidin. We have a set of programs that suppress hepcidin and associated programs that induce hepcidin and each have different uses in hematology. DISC-0974 is an antibody against a target called hemojuvelin or HJV that we in-licensed from AbbVie in 2019. It is given subcutaneously and, based on phase 1 data, it appears to be suitable for once monthly dosing. The Phase 1 data for DISC-0974 was recently presented at the European

Hematology Association, and showed promising evidence of activity, which I will go through later. We ve now opened a trial in patients with anemia of myelofibrosis, a severe and

difficult-to-treat form of anemia, and we are also working to open a trial in patients with anemia as a consequence of chronic kidney disease, focusing particularly on

the non-dialysis population. We expect to get data flowing from these two trials across 2023.

earlier pipeline programs as you can see here. The first is a follow-on molecule to DISC-0974 called DISC-0998 with an extended half-life, which is positioned for indication expansion as well as lifecycle

We have another discovery program against a compelling target called matriptase-2 and this would be

designed for treating polycythemia vera and also diseases of iron overload. There, we re in the discovery stage, working on our lead candidate optimization.

This next slide shows the Disc vision of growth. We ve established a track record of exceptional operational capability moving from a preclinical company

in 2019 to a company with multiple programs in patient trials here in 2022. As you can see, we are entering an exciting period in our company s story, which this financing will support.

So now I will turn to each individual program, starting with bitopertin.

This molecule is an inhibitor of glycine uptake through a transporter called GlyT1. What s interesting about glycine uptake is that it is fundamental for

red blood cell formation. Glycine is the first metabolite that s converted into heme, and heme, of course, is a critical component of newly forming red blood cells, so what has been shown in the clinic is that by suppressing glycine uptake

there s inhibition of the flow of metabolites through the heme biosynthesis pathway. The objective is to use this mechanism to address diseases where the heme biosynthesis pathway is driving disease.

First and foremost are diseases called the porphyrias. These are diseases caused by the accumulation of toxic porphyrins, which are intermediate metabolites in

heme biosynthesis that accumulate to toxic levels in these patients. In particular, we are focusing on two forms of porphyria, erythropoietic protoporphyria and X-linked porphyria, or EPP and XLP. For brevity,

throughout this talk, I have referred and will continue to refer to both of these together as EPP. As we announced earlier today, the Phase 2 BEACON trial is open and recruiting in these two forms of porphyria, and then we expect to expand from

there to disorders caused by heme toxicity, disorders caused by hemoglobin toxicity and those caused by an excess of red blood cells.

that s up and running is in patients with EPP, which is a rare debilitating lifelong condition characterized by extreme pain and damage to skin caused by sunlight. It is a genetic condition driven by a toxic metabolite called protoporphyrin IX,

or PPIX, which, as I mentioned earlier is a metabolite of the heme biosynthesis pathway. In addition to the skin phototoxicity, the other major symptom of disease is hepatobiliary complications with gallstones, liver dysfunction, and in some cases

liver failure and death. There are also substantial psychosocial issues that these patients face.

Today, there is only one FDA approved agent, a

surgically implanted agent called afamelanotide that stimulates skin pigmentation or tanning and thereby causes some resistance to sunlight. From a patient prevalence point of view, there are approximately

7,000-8,000 EPP and XLP patients in the US and Europe. These numbers represent identifiable patients, but recent genetic studies suggest that there may be additional patients who have not been properly

diagnosed. This is a disease that impacts multiple aspects of patients lives, and the impacts are severe, even leading to fatalities.

shares testimonials from patients of a variety of ages and their caregivers illustrating the degree of pain and lifestyle impacts that EPP patients face.

So again this disease is driven by the molecule shown in the center of the slide, protoporphyrin IX. This is produced by the heme biosynthesis pathway and

accumulates due to mutations in that pathway in these patients. This ring structure leads to absorption of light energy and as that energy is released inside the body, it causes intense pain in the skin. This molecule also accumulates in the bile

canaliculi, leading to significant rates of liver damage and gallstone formation as well as a small percentage of liver failure and even fatality.

again this disease is caused by mutations in the first or last enzymes of the heme biosynthesis pathway and those genetic defects leads to the buildup of the metabolite PPIX. Our hypothesis is that by reducing the flow of glycine into the top of the

heme biosynthesis pathway, we can reduce the amount of PPIX and this would have the potential to be the first disease modifying treatment for EPP.

have been able to run a variety of pre-clinical models ourselves and with collaborators at Boston Children s Hospital and this data has all been presented at various scientific conferences. As a quick

summary, in cellular models of EPP where we introduced the disease causative mutation, we see a dramatic dose response decrease in PPIX levels and then in two different mouse models we see decreases in PPIX of 45 to 73% depending on the model

that s run. Based on several clinical publications, we expect a 30% percent or greater decrease in PPIX to really cause significant modification of all aspects of the disease. I should also mention that our collaborators have observed that, in

mouse models, bitopertin reduced liver fibrosis as well, which is an expected consequence so the available pre-clinical data suggests that by reducing the flow of glycine into the heme biosynthesis pathway we

can achieve what appears to be a meaningful impact.

We in-licensed bitopertin from Roche, which had failed Phase 3 trials in neuropsychiatric indications but in that

process Roche had established a thorough package in anticipation of commercialization. So we are the beneficiaries of extensive non-clinical, CMC, and clinical information including a safety profile collected

in over 4,000 patients and 30 clinical trials. Many late-stage risks have already been addressed like carcinogenicity studies and long-term toxicology, so we do not expect to face problems on these aspects of the program.

We are up and running now with the BEACON trial. This is an open label Phase 2 trial where we re looking at two dose groups 20 mg and 60 mg once

daily for six months plus a potential extension. These doses bracket where we saw efficacy in the mouse models and are predicted to reach 70-90% target engagement in humans. The primary endpoint will be

changes in PPIX levels and secondary endpoints will include the clinically relevant metrics of light tolerance as well as measures of hepatobiliary health. We expect to be able to report interim open label PPIX data from this trial as early as year-end 2022, ranging possibly to mid-year 2023, depending on the speed of enrollment and other factors.

We also plan to be opening a US trial called the AURORA trial soon. This is a randomized double-blind placebo-controlled study in approximately 75 patients.

Here we ll have three arms placebo plus the same 20 and 60 mg once daily doses over a four month period. This will give us a placebo-controlled data set to design a pivotal trial.

Collectively we think we ve made great progress on this program since we in-licensed it from Roche in 2021.

We ve completed the GMP clinical supply, we ve opened the BEACON trial, we plan to open the AURORA trial in the coming months, and we expect to have data flow in the next 6 to 12 months for both trials. We re also working on a Phase 2

trial in Diamond Blackfan anemia through an investigator-initiated mechanism and, as I mentioned earlier, we believe this mechanism has potential across many different additional indications that we are looking forward to exploring.

Now let me turn to our iron metabolism program. These were the founding programs of the company.

It is well known that a hormone-like molecule called hepcidin is the key gatekeeper for iron in the body. Normally, about 70% of your iron is in your red

blood cells and there s a tremendous flow of iron from the stores in the spleen to enable new red blood cell formation. Of course, iron comes into the body from the diet through the G.I. tract as well. Both of these processes are regulated by