By Mike Cloonan, Chief Executive Officer of Sionna Therapeutics, as part of the From The Trenches feature of LifeSciVC
The drug development process in rare diseases is rife with challenges especially when companies target significant differentiation or first-in-class targets. Identifying the right targets, de-risking those targets, and then executing trials requires significant capital, strategic focus, and time. Reaching the end goal of delivering transformational new treatment options for patients can take a decade or more even when companies execute successfully and are well capitalized.
If we in the industry can find creative ways to accelerate and de-risk this process, it could have tremendous benefits for families affected by rare diseases and lessen the time they are waiting for new treatment options. It could also encourage more investment in the space and make us better partners to regulators and payors alike.
It’s important to recognize that for many large pharmaceutical and biotechnology companies, compounds that have the potential to treat a rare disease of significant unmet need might become lower strategic priority than those that have mass market potential. And many that have solid preclinical and even clinical data are left on the shelf due to portfolio prioritization processes or because the therapeutic area is no longer core to that company’s strategy. At Sionna, we have capitalized on this exact dynamic to strengthen our portfolio of assets that could potentially accelerate our development efforts while also enhancing the strategic optionality of our pipeline.
Sionna’s founding was directly related to a change in strategy at a big pharma that opened the door to create a company that could uniquely focus on cystic fibrosis. We are building on over a decade of extensive research on the genetic mutations associated with cystic fibrosis that originated at Genzyme and then continued at Sanofi, where our founding scientists discovered first-in-class correctors that in preclinical studies directly stabilized the first nucleotide-binding domain (NBD1) of the CFTR protein.
NBD1 has long been considered the “holy grail” target in cystic fibrosis that has been considered “undruggable.” Our development strategy is to build a cystic fibrosis franchise anchored on these novel stabilizers of NBD1. Combining our stabilizers with just one complementary CFTR corrector has the potential to deliver superior efficacy over the current standard of care and could significantly impact the lives of so many people living with cystic fibrosis and their families.
We already have the first-ever clinical-stage NBD1 stabilizer and a second series of highly potent NBD1 stabilizers that are advancing to Phase 1 this summer. In parallel, we’re developing our own complementary correctors to enable combination therapies, with multiple candidates targeting different regions of the CFTR protein, including one that is currently in an ongoing Phase 1 clinical trial.
While we are excited by the progress we have made in a short time, we also considered how we could possibly further accelerate and de-risk our development efforts.
We knew AbbVie had pursued development programs in cystic fibrosis for a long period of time – long enough to advance some of their CF compounds through Phase 2 trials before making a strategic decision to move away from cystic fibrosis. In Phase 2 clinical trials, ABBV-2222 in combination with ABBV-3067 demonstrated clinical efficacy, including increased percent predicted forced expiratory volume in 1 second (ppFEV1) and reduced sweat chloride (SwCl) levels, in a way that is comparable to approved dual modulator combinations.
We believe that targeting NBD1 in combination with the AbbVie compounds could potentially deliver a superior treatment option for CF patients over the current standard of care. Fortunately, AbbVie felt the same way, which is why we initiated discussions to in-license AbbVie’s most promising CF pipeline programs. During the diligence process, in pre-clinical assays we performed, including the Cystic Fibrosis Human Bronchial Epithelial (CFHBE) assay, dual combinations of a Sionna NBD1 stabilizer and just one complementary AbbVie modulator demonstrated the potential for superior efficacy over the current standard of care. Some combinations have the potential to achieve wild type levels of CFTR function, which could be highly differentiated and a significant improvement for people living with cystic fibrosis.
The potential of combining Sionna and AbbVie assets in our efforts to create best-in-class combination treatment options for CF patients was the driver of executing the license agreement with AbbVie, which significantly expands and accelerates our pipeline of complementary modulators to combine with NBD1. We obtained exclusive worldwide rights to develop and commercialize multiple clinical-stage compounds, including two that have completed Phase 2 studies. We have the deep experience in cystic fibrosis and sharp focus that is necessary to advance the development of these compounds continuing the strong efforts by AbbVie over the last several years. AbbVie will continue to have interest in the programs through late-stage development and commercial milestones and royalties.
We obtained rights to these compounds to de-risk and accelerate our development strategy with multiple options for potentially transformational combinations aimed at fully normalizing CFTR function. We will now have seven clinical stage assets with the opportunity to prioritize advancing one of the AbbVie compounds, with Phase 2 data in hand, as a potential dual combination option with one of our NBD1 stabilizers. We are well-positioned to execute our differentiated dual combination development path with the goal of providing more efficacious treatment options for people with cystic fibrosis.
We struck quickly to secure these assets as soon as AbbVie announced that cystic fibrosis was no longer a strategic area of focus. Specialty companies can play an important role in accelerating clinical development, especially in rare diseases like cystic fibrosis by being strategically opportunistic and moving quickly. Keep an eye out for compounds that may have been abandoned for strategic reasons, have compelling data, and have significant potential to address unmet needs in the hands of a highly focused company able to advance the programs. Such deals can create a win-win-win for patients, the licensee, and the licensor, leveraging years of development and capital investment while potentially accelerating the time to approval. This approach can lead to enhanced strategic optionality and the opportunity to prioritize the best compounds from a portfolio that can create meaningful paths to success. It takes knowing where to look and being ready to strike when those potentially company-enhancing assets become available.
===
