– Phase II secondary data confirmed remarkable potency of ATB-346 –
– 3rd party commercial studies project peak annual sales of $5.3 billion across seven key countries –
– Large market partnering efforts to accelerate in parallel with Phase III program –
– Non-opioid painkiller advancing towards the clinic; pipeline expansion initiatives underway –
TORONTO, CANADA — (August 4, 2020)
To our shareholders,
As we transition into a Phase III company, we want to take the opportunity to highlight recent progress and to outline our strategy as we pursue monetization of our promising drug candidates and hydrogen sulfide platform.
RECENT DEVELOPMENTS
Analysis of Phase II Dose-Ranging, Efficacy Data Now Complete
Having completed the analysis of primary and secondary data from ATB-346’s recent placebo-controlled efficacy trial, we can confidently report strong results across all key measures.
The WOMAC pain scores constituting the study’s primary endpoint showed 44% improvement from baseline at day 14 for the 200 and 250 mg once-daily doses, and 39% for the 150 mg once-daily dose. NSAIDs typically reach their maximum effectiveness after 6-8 weeks of administration and remain at that level while treatment continues. ATB-346 produced significant decreases in pain within 2 weeks of treatment. All three doses of ATB-346 reflect well in light of results from a recent peer-reviewed meta-analysis of historical NSAID osteoarthritis pain trials from Harvard researchers[1]. (For further information, please see our website and updated Corporate Presentation).
Beyond the impressive pain relief, ATB-346 also delivered significant improvements in the two secondary endpoints that address therapeutic benefit for patients: the WOMAC scores for stiffness and for difficulty in performing daily activities. These results are important, ‘real-world’ measures for patients with osteoarthritis (“OA”) and provide additional support for the drug’s best-in-class positioning.
Supplementing the WOMAC results are the secondary data of cyclo-oxygenase (“COX”) enzyme inhibition. NSAIDs reduce pain and inflammation by inhibiting the activity of COX enzymes. ATB-346 exhibited profound inhibition of COX (all doses yielding >90% inhibition) with a very high degree of statistical significance, and with negligible difference observed across the three doses. This is exceptionally strong data that is consistent with self-assessment of pain by the patients.
Adverse events across the three doses of ATB-346 were similar to placebo, with very few serious adverse events or events leading to withdrawal of treatment. Adjudicating for patient-specific factors reflected a liver safety profile for ATB-346 that was comparable to commonly prescribed NSAIDs, and substantially improved over that of acetaminophen.
Trial participants treated with ATB-346 experienced neither an increase nor decrease in blood pressure in contrast with other NSAIDs, which often increase blood pressure. Blood pressure increases are viewed by medical practitioners globally as being an important proxy for the cardiovascular risk of NSAIDs. The absence of an increase in blood pressure has been a consistent finding in all of ATB-346’s clinical trials to-date and suggests a favourable cardiovascular safety profile for the drug.
Human Proof-of-Concept Now Firmly Established for ATB-346
The strong Phase II efficacy results from this trial are a worthy complement to Antibe’s Phase II gastrointestinal (“GI”) safety trial, published last year in the British Journal of Pharmacology[2]. That study demonstrated unequivocal GI safety superiority of ATB-346 over naproxen, one of the most prescribed NSAIDs in the US. This combined evidence for GI safety and efficacy firmly validates ATB-346 as a potential best-in-class therapy, indicating that we are on the verge of solving one of the most pervasive medical problems of our time, namely the ulcers and bleeding caused by NSAIDs.
Third Party Commercial Studies Validate Blockbuster Potential of ATB-346
In addition to completing strong GI safety and efficacy studies over the past two years, we have conducted an extensive series of market and commercial studies in key pharmaceutical markets — a total of four studies were completed, framing an impressive commercial opportunity for ATB-346 and preparing us well for late-stage partner engagement and monetization.
This effort began with a thorough health economics study led by US-based Avalon Health, quantifying the major economic impact to society arising from the damage caused by today’s NSAIDs. A subsequent commercial positioning study executed by an ex-Amgen strategy consulting team validated ATB-346’s target product profile and best-in-class positioning.
The results of these two initial studies served as the foundation for two comprehensive commercial studies for the large markets (namely, the US, the five largest European countries, and Japan), led by Shift Health and LEK, two well-respected strategy consultancies. These studies involved extensive primary and secondary research, including 62 interviews with country-specific clinicians, payors and pharmacy benefit managers – whose preferences and policies together determine the adoption of new drugs. This was followed by an in-depth survey of 80 clinicians, including primary care physicians, rheumatologists and orthopedic surgeons that prescribe NSAIDs on a daily basis. Finally, the studies developed detailed revenue models, utilizing the uptake and pricing information obtained from the research and interview phases of the project.
For the OA market alone, Antibe’s initial focus, peak annual sales of $5.3 billion are projected for ATB-346 in these seven countries, and cumulative revenues in excess of $28 billion by the early 2030s. These projections conservatively assume peak adoption of 21% and only represent 65% of the global market. Pricing and reimbursement, which drive a drug’s adoption and ability to gain market share, were favourable, with limited system resistance and few reimbursement hurdles expected. The forecasts assumed a price of US$6 per day in the US, in line with today’s branded prescription NSAIDs, with corresponding pricing in the other markets. The revenue projections combined with a high anticipated gross margin imply an impressive net present value of ATB-346, which is how potential partners determine a drug’s expected value. (For further information, please see our website and updated Corporate Presentation).
STRATEGY AND NEXT STEPS
With human proof-of-concept development and key commercial studies complete, we now have a clear line-of-sight to the significant revenue and margin potential of ATB-346. Our strategic objective is now to monetize this asset through partnering activity, while at the same time expeditiously moving forward with Phase III development. This parallel strategy is important, as partnering outreach and execution is an extensive, involved process, and the continued advancement of the drug’s development program is expected to increase market value and negotiating leverage.
Executive Team Evolving to Support Late Stage Development and Partnering
We continue to deepen the capabilities of our senior team, including the recent hiring of Dr. Rami Batal to guide our commercial strategy, and Dr. Joseph Stauffer as the Company’s Chief Medical Officer. Dr. Stauffer’s experience as an FDA reviewer, along with more than fifteen years of guiding regulatory strategy for other pain therapeutics, has already been invaluable as we pursue our regulatory, development and commercial strategies in the US and other markets. We are also hiring a US-based senior business development officer to execute the large market partnering, who will be armed with fully validated human proof-of concept data and a robust package of third-party commercial assessments.
Strategic out-licensing and monetization discussions are underway and have benefited from the strength of the recent efficacy data, while partnering discussions in the major markets are expected to accelerate following specific regulatory engagement with both the Food and Drug Administration (“FDA”) in the US and the European Medicines Agency (“EMA”) in Europe. We are encouraged by the preliminary feedback and hope to report on the progress on this front over the coming months.
Phase III Preparation and Regulatory Strategy Well Underway
With the successful conclusion of ATB-346’s Phase II studies and acceleration of partnering activities, preparation for Phase III trials is well underway. The Phase III program will replicate the Phase IIB GI safety and dose-ranging, efficacy studies with larger sample sizes and longer treatment durations. The first registration trial of the Phase III program will use a multi-arm design to establish the lowest effective dose and is anticipated to begin next spring, with the follow-on trials starting in a staggered fashion every several months thereafter. The strategy is global in nature, with the first trials focusing on the US and the last trial expected to address the unique regulatory requirements for Europe and the key Asian markets. The go-to-market indication will be OA, although we intend to rapidly expand this to encompass ankylosing spondylitis, rheumatoid arthritis and other chronic pain conditions. It is worth noting that successful completion of Phase III development would enable the Company to file a New Drug Application (“NDA”) with the FDA and other regulatory agencies for marketing approval. This approval would deliver the first truly novel NSAID in over 20 years, and a major breakthrough in the safe and non-addictive treatment of pain and inflammation.
As part of Phase III preparation, we completed our Pre-IND (“Investigational New Drug”) meeting for ATB-346 with members of the US FDA Division of Anesthesiology, Addiction Medicine, and Pain Medicine. Based on the valuable guidance received, we are moving expeditiously to complete and submit an IND application to the FDA for ATB-346. Prior to the start of the first Phase III trial, we anticipate an End-of-Phase II Meeting with the FDA and the equivalent meeting with the EMA, which will strengthen Antibe’s position with potential large market partners.
We are pleased to have recently received approval for ATB-346’s International Nonproprietary Name: otenaproxesul. (The non-proprietary name is equivalent to, for example, the “ibuprofen” of Advil®). We will be using otenaproxesul going forward, and our Corporate Presentation and website have been amended as such. In addition, we have now engaged a healthcare branding agency to help us select a proprietary (brand) name (the equivalent to “Advil®”).
ATB-352 Advancing Towards Clinical Development Next Year
Expanding beyond our lead drug, we have commenced IND-enabling preclinical studies for our second pipeline drug, ATB-352. This drug is being developed as a GI-safe and non-addictive alternative to opioids for the treatment of post-surgical pain, a US$11 billion market[3]. Many physicians find themselves in a quandary regarding opioids, which have been the drug-of-choice for post-surgical pain. The natural alternative would be the stronger NSAIDs, already shown to equal the pain relief of opioids in such settings. However, such NSAIDs are also the most harmful to the digestive tract. ATB-352, a hydrogen sulfide-releasing version of ketoprofen (a particularly strong NSAID), is being developed as a solution to this longstanding problem. In animal experiments, ATB-352 has delivered greater pain effectiveness than ketoprofen yet demonstrated robust GI safety. We anticipate that preclinical studies of ATB-352 will conclude in calendar Q3 2021, following which we will seek regulatory approval to initiate human trials. We plan to pursue a Fast Track designation with the FDA to expedite the development and regulatory approval process.
Our third pipeline drug, ATB-340, a hydrogen-sulfide releasing version of low-dose aspirin, has been shown to cause negligible GI damage in preclinical studies. Low-dose aspirin is generally regarded as a wonder drug for cardiovascular and cancer protection for people over 50, but its prevalence of GI-damage precludes its broad prescription by clinicians. We are presently evaluating the clinical development strategy for ATB-340 and anticipate commencing IND-enabling preclinical studies in calendar 2021.
Pipeline Expansion Initiatives Launched
The strength of the recent clinical data has also encouraged us to commit to unlocking additional value from our hydrogen sulfide platform. To this end, Antibe recently signed a contract with a leading academic institution in the US known for the quality of its hydrogen sulfide science. The objective of this mandate is to identify promising new hydrogen sulfide-releasing compounds for the treatment of chronic pain, acute pain and other indications, including inflammatory bowel disease. Antibe will retain ownership rights to any new intellectual property arising from this work.
In addition, we are exploring collaborations for additional indications for otenaproxesul, including familial adenomatous polyposis (FAP), a pre-cancerous and often-fatal orphan disease.
Capital Markets Strategy Taking Institutional Focus
The success of otenaproxesul over the past few years has increased our valuation and de-risked our story considerably – this could not have been done without the long-term support of our existing shareholders. The last several months culminated in significant achievements, including a $29 million bought deal financing, that position us well to crystalize the value of our efforts. While we believe the issue price did not reflect the opportunities before us, the financing was essential for executing our plans in the coming 15 months at full speed with a fully funded balance sheet. We will now be pursuing a capital markets strategy to support our next stage of growth, while enabling our share price to reach an inherent value that is more comparable to our Phase III peers.
The completion of human proof-of-concept development for otenaproxesul with such strong results has put us on the radar screens of institutional investors that will be instrumental in supporting this growth. Preparations are largely complete to list on a senior exchange at the optimal time, such as NASDAQ. In addition, we will shortly engage a premier life science-focused investor relations firm in the US to implement and lead a strategic outreach program towards institutional investors, sell-side analysts and bankers.
We are in the process of evaluating a potential sale of Citagenix, our commercial asset that is no longer a strategic fit. This will simplify our story into a “pure play” late-stage biotech company with a clear focus and growth trajectory. And as we attract more institutions and mature as an organization, we will correspondingly require more active and deepened governance to guide our decision-making. We have retained a specialized recruitment firm to help us find a new, US-based Board member, whom we expect to have in place by year end.
We are excited by the opportunities ahead, as we strive to unlock shareholder value and execute our strategy over the course of the coming year.
Sincerely,
Dan Legault
Chief Executive Officer
[1] Comparative Pain Reduction of Oral Non-steroidal Anti-inflammatory Drugs and Opioids for Knee Osteoarthritis: Systematic Analytic Review. Osteoarthritis and Cartilage. S.R. Smith et al., 2016.
[2] A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug. British Journal of Pharmacology. Wallace et al., 2019.
[3] Transparency Market Research, 2018.
About Antibe Therapeutics Inc.
Antibe develops safer, non-addictive medicines for pain and inflammation. Antibe’s technology involves the linking of a hydrogen sulfide-releasing molecule to an existing drug to produce an improved medicine. Antibe’s lead drug, ATB-346, targets the global need for a safer, non-addictive drug for chronic pain and inflammation. ATB-352, the second drug in Antibe’s pipeline, targets the urgent global need for a non-addictive analgesic for treating post-surgical pain, while ATB-340 is a GI-safe derivative of aspirin. Citagenix Inc., an Antibe subsidiary, is a market leader and worldwide distributor of regenerative medicine products for the dental marketplace. www.antibethera.com.
Forward Looking Information
This news release includes certain forward-looking statements, which may include, but are not limited to, the proposed licensing and development of drugs and medical devices. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking, including those identified by the expressions “will”, “anticipate”, “believe”, “plan”, “estimate”, “expect”, “intend”, “propose” and similar wording. Forward-looking statements involve known and unknown risks and uncertainties that could cause actual results, performance, or achievements to differ materially from those expressed or implied in this news release. Factors that could cause actual results to differ materially from those anticipated in this news release include, but are not limited to, the Company’s inability to secure additional financing and licensing arrangements on reasonable terms, or at all, its inability to execute its business strategy and successfully compete in the market, and risks associated with drug and medical device development generally. Antibe Therapeutics assumes no obligation to update the forward-looking statements or to update the reasons why actual results could differ from those reflected in the forward-looking statements except as required by applicable law.
Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.
Contact Information
Antibe Therapeutics Inc.
Christina Cameron
VP Investor Relations
+1 416-922-3460
[email protected]
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