Advancing Viral Disease Treatment of Recurrent Genital Herpes, Hepatitis B and D Viruses

Hepatitis B virus

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Herpesviruses, hepatitis B, and hepatitis D can be severe viral diseases, and patients still need more treatment options. But how can different treatments help bring better patient outcomes?

While the CDC provides information on hepatitis B virus (HBV), hepatitis D virus (HDV), and genital herpes for health care professionals, new therapies are needed.

In this exclusive interview with Infection Control Today^® (ICT^®), Jason Okazaki, CEO and president of Assembly Bio, discusses the company's pioneering efforts in revolutionizing the treatment paradigm for severe viral diseases. With a focus on addressing unmet patient needs, Assembly Bio's expanded pipeline targets recurrent genital herpes, HBV, and HDV, offering promising solutions to enhance patient outcomes. Okazaki elaborates on the challenges faced in research and development (R&D), strategic collaborations with Gilead Sciences, and the outlook for Assembly Bio in tackling viral infections.

ICT: Could you elaborate on the innovative therapies in Assembly Bio's expanded pipeline and how they address the unmet needs of patients with serious viruses like recurrent genital herpes, HBV, and HDV?

Jason Okazaki: We are focused on altering the treatment paradigm for serious viral diseases. All our programs target areas where there is a significant unmet patient need and where we see a clear opportunity to meaningfully improve patient outcomes.

For example, in high-recurrence genital herpes, only about one-third of patients taking the standard-of-care antiviral make it through a year of therapy without recurrence, and their transmission rates are only reduced by approximately 50%. We think we can drive these percentages much higher with our candidates, designed against the clinically validated helicase-primase target and shown much greater potency than the standard of care preclinically. Additionally, we have taken the unique approach of developing a long-acting compound that we believe will only require weekly oral dosing, relieving pill burdens for patients and greatly simplifying therapy. I would also note that our helicase-primase inhibitors are active preclinically against both herpes simplex virus (HSV)-1 and HSV-2, which gives us the potential to expand studies to address orofacial herpes as well as explore episodic and prophylactic therapies.

Treatment options are limited for (HDV), the most serious form of viral hepatitis, in which 70% of patients progress to cirrhosis in 10 years. The current standard of care, which is currently only approved in Europe, has demonstrated safety and efficacy in its clinical trials; however, it is a daily injectable that requires cold storage. Our HDV entry inhibitor candidate, ABI-6250, targets the same mechanism but as a small molecule therapy that we anticipate dosing as a once-daily pill.

We also continue to evaluate our highly potent next-generation capsid assembly modulator (CAM), ABI-4334, in chronic HBV as there remains a great need for a cure for the nearly 300 million people living with HBV globally.

ICT: What do you want infection prevention personnel to know about the fight against herpesviruses, HBV, and HDV?

JO: Much more can and should be done. There has been a significant lack of investment and focus on herpesviruses in particular, and that lack of focus has a profound impact on patients' lives.

Notably, the standard of care for genital herpes is more than 20 years old, with an urgent need for advancement. Additionally, serological tests for HSV need to be improved as they are currently underrecommended due to high false positive rates, which leads to fewer diagnoses and limits patients from receiving treatment that could benefit not only their life with the virus but also their overall quality of life.

HDV is also underdiagnosed in patients, in part due to the lack of treatment options. We hope and expect testing and diagnosis efforts to improve as more therapies come to market.

HBV is also significantly underdiagnosed, and while there are currently effective treatments on the market, the field is looking toward a cure. That effort is ongoing, and the scientific understanding of how to move the needle on cures is still in development.

We are passionate about our work to advance novel treatment options for individuals with these viral diseases and believe that our pipeline has the potential to meaningfully change treatment paradigms in each of these areas.

ICT: Can you share insights into Assembly Bio's recent challenges in its R&D and how the company navigated through these setbacks?

We continue to see in this industry that R&D is rarely linear, and scientific exploration requires constant learning from clinical successes and setbacks. At Assembly Bio, we hold ourselves to the highest standards of scientific rigor and have leveraged the insights from our progress and setbacks to develop a clear strategic path to addressing serious viral diseases with our optimized pipeline.

Assembly Bio historically has been a pioneer in developing CAMs for hepatitis B. Our first-generation CAM, vebicorvir, demonstrated safety and strong viral suppression in clinical studies but did not achieve a cure. Our next-generation CAM, ABI-4334, which is expected to start a Phase 1b clinical study by mid-2024, is 1,000 times more potent preclinically than vebicorvir against a key mechanism of action of CAMs that targets formation of the HBV reservoir, cccDNA. We applied several learnings from vebicorvir’s discovery and clinical data to optimize 4334’s activity against cccDNA and help guide the clinical path for that molecule.

Similarly, the company significantly evolved over the past 3 years as we drew upon the talents of our extraordinary team and deep virology expertise to expand our discovery and development efforts beyond HBV into herpesviruses and HDV. Those efforts yielded 2 candidate nominations in 2023: ABI-5366, our long-acting helicase-primase inhibitor for HSV, and ABI-6250, our small molecule entry inhibitor for HDV. We expect 5366 to enter the clinic by mid-2024 and 6250 by the end of 2024; we’ve made incredible progress on these programs in a short period. We are excited to progress multiple compounds in the clinic this year that can potentially change patients' lives.

ICT: The long-term partnership with Gilead Sciences is a significant development. How does this collaboration contribute to Assembly Bio's objectives, and how does it impact advancing therapies for recurrent genital herpes, HBV, and HDV?

JO: We are thrilled to partner with Gilead, as we believe the shared expertise and promising investigational therapies that both organizations contribute to this collaboration can potentially benefit patients. Gilead is a leader in virology, with whom we have a strong relationship, given that several members of our scientific leadership team previously worked there developing pioneering antivirals. Our companies are driven to succeed in herpesviruses and viral hepatology, and the support and collaboration between our organizations reflect that singular goal.

One unique part of the collaboration is that Gilead contributed 2 herpesvirus programs to us. We will leverage the learnings and progress of both companies to drive our efforts together with our existing programs. As a result, we’ve already seen benefits in these programs, illustrating the ability of this collaboration to greatly support our R&D efforts.

Further, the partnership is structured so that if Gilead opts into a program, we will have an ideal partner for the late-stage development and commercialization of these antiviral therapies. We’ll then have revenue in the form of option payments, regulatory and commercial milestones, and royalties to support and sustain our R&D. At the same time, we have the option to elect to profit and cost share (40% share) in the US. We can opt-in for copromotion for future programs. For programs that Gilead does not elect to opt into, we retain the rights to these programs to bring them forward on our own or repartner.

The Gilead partnership allows us to drive our R&D forward and grow and expand our commercial capabilities, better positioning us to bring products to market and fulfill our commitment to patients.

ICT: In the context of the broader virology landscape, what opportunities and challenges do you foresee for Assembly Bio as it works towards improving outcomes for patients with these viral infections?

JO: The programs we’re bringing forward now showcase the opportunity in virology to meaningfully advance therapeutics in herpesviruses and viral hepatitis. These opportunities also demonstrate how some of those areas, like genital herpes, have been underserved for many years and have not seen the concentration of drug discovery efforts we’ve seen in other therapeutic areas from the industry. We’ve demonstrated the depth and breadth of our virology discovery engine. As we look to move 4 compounds into the clinic by the end of this year, we are excited to start seeing the potential of these compounds unfold.

Of course, clinical trials are costly and take time to yield data, so, like any precommercial biotech, we maintain a close eye on our cash runway. We will evaluate additional funding opportunities as needed. Fortunately, our partnership with Gilead provided a tremendous scientific partner and significant funding to advance our programs; still, the need for ongoing funding remains a reality for small biotech companies like ours and is a challenge we all face.

ICT: As the driving force behind Assembly Bio's progress, what motivates you personally to lead the charge against herpesviruses, HBV, and HDV, and what do you envision for the company's future in tackling these challenges?

JO: Our scientific progress over the past few years has been a true team effort. We have the best team of virology experts I’ve seen, and we all motivate each other with a shared passion for advancing therapies to change people’s lives.

Certainly, the pandemic underscored the impact viruses can have on our lives and health, emphasizing the need for our industry to prioritize developing novel approaches that serve patients with serious viral diseases. It also highlighted the enormous effect the scientific and medical community can have. Unfortunately, most diseases do not receive the same global attention as COVID-19, nor are products developed as quickly. That’s why it’s so important for companies like us to work on novel therapies for diseases like herpesviruses, HDV, and viral hepatitis, as millions of patients in this world deserve therapeutic innovation.

As I look ahead toward the company’s future, I envision Assembly being successful not only with our current programs but also in utilizing our scientific expertise to continue developing our pipeline to target diseases with underserved or unserved patient populations. I look forward to seeing this team continue to do what it does best—innovating novel therapies.