Alkermes has been reimagining medicines to help improve the therapeutic experience for patients for more than 30 years. Its current research and development efforts are focused on the pursuit of potential new medicines that build on the company’s heritage in neuroscience and more recent advancement into immuno-oncology. The 2019 acquisition of Rodin Therapeutics has also expanded Alkermes' early-stage development efforts into a wider range of neurodegenerative disorders and cancers.
In this interview, Blair Jackson, COO, Alkermes, speaks with Informa Connect’s Xconomy to discuss the rationale behind Alkermes’ evolving strategy in neuroscience and oncology and the ambition to be a major innovator in the competitive pharmaceutical landscape.
Xconomy: What are the scientific underpinnings of Alkermes, and how have you seen those evolve over the years?
Blair Jackson: With our roots in formulation and drug delivery, we built our technical capabilities and product development expertise over the years through the development and acquisition of platform technologies, which we leveraged to develop multiple products for both ourselves and collaboration partners in a wide range of therapeutic areas. These products were based on three key principles: thoroughly understanding the dynamics impacting patient outcomes, identifying efficient and novel development pathways and providing a strong value proposition to the treatment community.
Utilizing these same principles, we turned our attention to the development of novel molecular entities with compelling value propositions, seeking potential first-in-class or best-in class opportunities in both neuroscience and oncology.
XC: What drove the decision to go into the immuno-oncology space?
BJ: Our entry into immuno-oncology was guided by our protein engineering capabilities. We are applying these technologies with the goal of developing novel proteins with favorable clinical characteristics that target validated biological pathways in life-threatening cancers with few or no treatment options.
Immunotherapy has been game-changing in the way cancer is treated, but unfortunately, many patients only see limited impact or no benefit at all. This paradox was our inspiration: How can we use our protein engineering capabilities, along with our scientific expertise, to help people with cancer?
We viewed high-dose interleukin (IL)-2 based therapy – an efficacious treatment for certain tumor types limited by a burdensome tolerability profile – as an ideal first target for our foray into immuno-oncology. Through protein engineering, we were able to develop an investigational cytokine designed to harness the efficacy of the IL-2 pathway, while mitigating the tolerability issues associated with IL-2 therapy. This molecule nemvaleukin alfa has potential to target a wide range of tumors.
XC: How is progress going with nemvaleukin alfa?
BJ: Nemvaleukin alfa, our engineered IL-2 variant immunotherapy, has shown encouraging initial clinical responses in our comprehensive ARTISTRY development program. We are seeing important progress across multiple studies, including both monotherapy and in combination treatment, and via multiple routes of dosing administration.
ARTISTRY-1 is an ongoing study evaluating intravenous dosing of nemvaleukin as a single agent and in combination with KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors. As a single agent, we have seen encouraging activity of nemvaleukin as monotherapy in patients with melanoma and renal cell carcinoma, the two tumor types for which high-dose IL-2 is approved.
We are encouraged by the monotherapy data to date in checkpoint-inhibitor-experienced patients with melanoma, which is an area of significant unmet need. In addition, nemvaleukin was recently granted orphan drug designation by the FDA for mucosal melanoma, which is an important milestone for the program and underscores nemvaleukin’s potential clinical utility in this tumor type.
In the combination part of the study, which includes several cancer types, we have seen encouraging responses in multiple difficult-to-treat tumors. But most notable has been the encouraging responses in platinum-resistant ovarian cancer (PROC) patients. PROC is an advanced form of ovarian cancer for which there are limited treatment options available, and no immunotherapy currently approved. Encouraged by our early responses in PROC, we recently announced a collaboration and supply agreement with Merck/MSD* to study the combination of nemvaleukin and pembrolizumab in this tumor type in a planned phase 3 study.
ARTISTRY-2 is investigating subcutaneous dosing of nemvaleukin. After completing the dose escalation phase of the study, we recently announced our recommended phase 2 dose for the SC administration and initiated the phase 2 efficacy expansion portion of the study. The expansion phase will examine the combination of subcutaneously administered nemvaleukin with KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors.
ARTISTRY-3 was initiated in August 2020 to evaluate the clinical and immunologic effects of nemvaleukin monotherapy on the tumor microenvironment of a variety of advanced, malignant solid tumors. This trial is currently recruiting patients and we look forward to providing updates in the near future.
Most recently, we announced initiation of ARTISTRY-6, a global phase 2 trial evaluating nemvaleukin monotherapy in mucosal melanoma and cutaneous melanoma.
Overall, we are encouraged by the emerging data from the ARTISTRY program. The safety profile of nemvaleukin appears to align with what we had set out to achieve. Early responses with both the IV and SC administrations support the potential utility of nemvaleukin in certain tumor types.
XC: What setbacks, if any, has Alkermes had with carrying out these trials due to COVID-19?
BJ: Despite the impact of COVID-19 on clinical trial enrollment more broadly across the sector, enrollment in the ARTISTRY development program has accelerated overall. We believe these enrollment trends are an important indicator of investigator enthusiasm around the program.
XC: What was the thinking behind the Rodin acquisition and what is the connective thread with your current R&D portfolio?
BJ: The Rodin acquisition was driven by a convergence of several factors: our deep commitment to improving the lives of people with complex CNS disorders; our expertise in molecular design, and our R&D philosophy to target well-validated biological pathways.
Synaptic loss is currently a strong pathologic correlate with cognitive decline. Therefore, improving synaptic function may potentially slow progression and preserve cognitive and functional abilities, and may have broad applicability in neurological disorders.
Previous studies have shown that inhibition of histone deacetylases (HDACs) can result in increased synaptic density, but therapeutic applicability using first-generation HDAC modulators in chronic neurologic conditions has been limited by toxicity issues and low brain exposure.
Our HDAC inhibitor platform, which we acquired from Rodin Therapeutics, offers an elegant translational approach through selectivity. Our first development candidate from this platform (ALKS 1140) is believed to selectively inhibit the HDAC-CoREST complex and has shown minimal hematological effects in preclinical assessments and desired brain permeability.
XC: What is driving your future partnership and business development strategy and how is that authentic to Alkermes? What is the future of your M&A activity, and in which areas?
BJ: We are always talking to other companies about our assets, both within oncology and neuroscience. We use these interactions to keep the companies informed about the progress of our pipeline candidates and to engage in specific business discussions.
Alkermes was built on a platform of strong business transactions, and we seek partnerships for a wide variety of reasons: to offset the expense, to access certain expertise or resources that are unavailable to Alkermes or to expedite the development timeline of a program.
We have deep relationships with executives in many of the leading pharmaceutical companies, and it’s through these relationships and frequent interactions that potential partnerships may arise. When a deal is announced, it has often resulted from many months or years of discussions between the companies, so starting early is always a good idea.
If the right partnership structure and business partner are identified, we consider partnerships that can maximize the value of an asset or mitigate the risk profile of the company, or ideally both.
XC: Where does Alkermes see itself in the wider pharmaceutical landscape? Where does it aim to be five years down the road?
BJ: In five years, we hope that Alkermes will be viewed as an innovative company with deep scientific expertise bringing novel medicines to market that address unmet needs for difficult-to-treat diseases. We also hope that our translational medicine approach will allow us to make early and smart scientifically informed decisions that add value for our shareholders and make a significant difference to patients and the doctors who treat them. Finally, we’d like to be seen and known as a company that puts patients at the core of everything we do.
Alkermes is a unique company in the biopharmaceutical industry. We have a substantial and growing business with a portfolio of approved drugs and established drug development and commercialization capabilities. In the years to come, we see exciting future growth opportunities based on our new neuroscience and oncology product candidates in development.
Our goal is to focus our research programs on designing new molecules based on established biology rather than testing new biological hypotheses. Leveraging our advanced medicinal chemistry and protein engineering capabilities along with a disciplined, integrated research and commercial approach, we seek to develop products designed to make a meaningful difference in the way people manage their diseases.
* a tradename of Merck & Co., Inc. Kenilworth, NJ, USA