On Course: 2019 Annual Report

Shareholder letter

Daniel Gold, PhD

President and Chief Executive Officer

This past year we’ve remained on course, executing a straightforward, purposeful strategy to advance our pipeline of four clinical-stage oncology candidates and build a strong foundation to deliver value to our stakeholders.

ME-401:

ME-401 is an oral, once-daily, selective phosphatidylinositol 3-kinase (PI3K) delta inhibitor in clinical development for the treatment of B-cell malignancies. MEI owns worldwide rights in all countries except Japan, which we licensed to Kyowa Kirin Co. in 2018.

Voruciclib:

Voruciclib is an orally administered cyclin-dependent kinase (CDK) inhibitor differentiated by its potent in vitro inhibition of CDK9, in addition to CDK6, 4 and 1. The CDK family of proteins are important cell cycle regulators and CDK9 specifically has potential importance for treating certain B-cell and myeloid malignancies.

ME-344:

ME-344 is our novel and tumor selective, isoflavone-derived mitochondrial inhibitor drug candidate. It directly targets the OXPHOS complex 1, a pathway involved in ATP production in the mitochondria. Inhibiting ATP production via the mitochondria has potential to treat a wide variety of cancers, particularly in combination with other cancer therapies.

Pracinostat:

Pracinostat, which we licensed to Helsinn Healthcare, is an oral histone deacetylase (HDAC) inhibitor being evaluated in a pivotal Phase 3 global registration clinical trial for the treatment of adults with newly diagnosed acute myeloid leukemia who are unfit to receive intensive chemotherapy. Pracinostat is also being evaluated in a Phase 2 trial in patients with high or very high-risk myelodysplastic syndrome.

Dear Shareholders

This past year we’ve remained on course, executing a straightforward, purposeful strategy to advance our pipeline of four clinical-stage oncology candidates and build a strong foundation to deliver value to our stakeholders. The path we’ve charted has a clear destination: the delivery of benefit to patients with cancer beyond what is currently achieved through existing therapies.

To arrive at our destination, we are focused on executing on our corporate goals and strategy. Currently, our main focus is on ME-401, an oral inhibitor of PI3K delta, which continues to demonstrate high activity and improved tolerability via our innovative intermittent dosing regimen in patients across different B-cell malignancies. Based on ME-401 clinical data, we initiated our global Phase 2 study, called TIDAL, which may support an accelerated approval of a marketing application with FDA for patients with follicular lymphoma. Follicular lymphoma, and B-cell malignancies more broadly, are generally not curable and there continues to be a significant need for new treatments.

We also entered a clinical collaboration with BeiGene, Ltd. to combine ME-401 with zanubrutinib, BeiGene's investigational BTK inhibitor. Importantly, we also completed a regional licensing deal with Kyowa Kirin Co., Ltd. for the development and commercialization of ME-401 in Japan. The more we study ME-401, the stronger we believe we have the opportunity to open a new chapter in the utility of PI3K delta inhibitors, particularly in combination with other therapies, to treat B-cell malignances.

Across the other programs in our pipeline, we reported promising data and made important advances in our development plans. Voruciclib, our orally available CDK inhibitor with potent inhibition of CDK9, an important regulator of cell survival signaling, has advanced in its Phase 1 study evaluating patients with hematological malignancies. The trial is initially studying voruciclib primarily for safety as a monotherapy in patients with relapsed or refractory B-cell malignancies or acute myeloid leukemia. Once establishing initial safety, we plan to evaluate voruciclib in combination with Venclexta® to confirm synergies observed in preclinical studies and to advance the opportunity for combination treatments across multiple indications.

Next is ME-344, our novel and tumor selective mitochondrial inhibitor, which is understood to block ATP production in the mitochondria. ATP is a source of energy for many cell processes. We reported promising results this past year from a clinical trial in women with breast cancer showing that when ME-344 is given in combination with Avastin® there was significant evidence of biologic activity demonstrating reduced tumor proliferation.

Our fourth drug candidate is pracinostat. As you know, it’s fully partnered with Helsinn Healthcare under an exclusive worldwide license, development, manufacturing and commercialization agreement. Pracinostat is an oral HDAC inhibitor being evaluated in a pivotal Phase 3 global registration trial for the treatment of adults with newly diagnosed acute myeloid leukemia who are unfit to receive intensive chemotherapy. Pracinostat is a promising candidate that was granted Breakthrough Therapy Designation by FDA, has Orphan Drug Designation from the EMA, both for the treatment of acute myeloid leukemia, and which is also being evaluated in a Phase 2 trial in patients with high or very high-risk myelodysplastic syndrome.

Looking back over the path travelled this past year, we believe we achieved several important milestones, delivering progress across our diverse set of drug-candidates, including two candidates in global studies to support marketing authorization.

In the year ahead, we plan to stay the course, maintaining focus on execution across the pipeline, exploring additional collaboration and licensing opportunities to most effectively leverage the potential of our drug candidates for patients, and building value for our shareholders.

Daniel Gold, Ph.D.

President & Chief Executive Officer

September 19, 2019

Nasdaq Spotlight Interview: Hear Dan Gold talk about MEI and it’s pipeline of oncology drug candidates.