A Seattle-based biotech developing innovative treatments for cancer and autoimmune/inflammatory diseases secured a $60 million cash payment and up to $805 million in potential drug development, regulatory and commercial milestone payments from major pharmaceutical company AbbVie. Publicly traded via a reverse merger, Alpine Immune Sciences (NASDAQ: ALPN) positions itself as a leading clinical-stage immunotherapy company that was able to negotiate an important drug development and commercialization collaboration deal involving an exclusive worldwide option and license agreement for their proprietary lead compound, ALPN-101. Based on the financial track record thus far, the deal looked like the smart thing to do.
TrialSite News offers a brief breakdown of this deal for the TrialSite Network.
What is the ALPN-101?
This investigational product known as ALPN-101 is positioned as a first-in-class dual CD28/ICOS constimulation antagonist. CD28 and ICOS are key costimulatory molecules that likely play critical roles in multiple autoimmune and inflammatory diseases. ALPN-101 is a potent inhibitor of both CD28 and ICOS pathways with demonstrated efficacy in multiple preclinical disease models, superior to blockage of either pathway alone. Favorable safety and tolerability, pharmacokinetics and pharmacodynamics have been observed in first-in-human study in adult healthy volunteers.
According to Alpine’s website, they have demonstrated ALPN-101’s superiority to FDA-approved therapies in several in vivo models of disease including GVHD and lupus. They list a series of scientific publications here. As far as actual clinical trials, ALPN-101 completed enrollment of a Phase I healthy volunteer study in October 2019. Initial data was presented at the American Society of Hematology annual meeting in December 2019 and more data from this Phase I trial are expected in 2020. Note, the study is called ‘BALANCE’, a Phase Ib/II trial in acute GVHD is open for enrollment.
What is their scientific proprietary Directed Evolution Platform?
This platform helps convert native immune system proteins into differentiated, multi-targeted therapeutics potentially capable of modulating the human immune system and significantly improving outcomes in patients with serious diseases. Their scientists use “directed evolution” or an iterative scientific engineering process, to purposefully modify native proteins for a desired therapeutic function.
What is the Intellectual Property behind Alpine Immune Science’s investigational products?
According to their SEC disclosures, substantially all of ALPN’s intellectual property has been developed internally. By the end of 2019, they had a patent portfolio of over 100 pending patent applications. Their initial patent platform is directed to their core scientific platform. Their second set of patent applications are directed toward the “TIP” program.
Why did AbbVie partner with ALPN?
AbbVie considers ALPN a leader in developing and commercializing innovative immunology therapies. AbbVie is looking to bolster immunotherapy options and the two will initially focus on working to transform outcomes in systemic lupus erythematosus, a disease with few treatment options.
AbbVie appreciates the potential for ALPN-101 based on the dual mechanism of action and will initially target systemic lupus erythematosus (lupus) and other autoimmune diseases.
What are the deal terms?
Alpine will receive a $60 million upfront payment and will be eligible in the aggregate of $805 million for exercise of a stock option (part of deal) and success-based development, regulatory and commercial milestones. Additionally, APLN will be eligible for tiered royalties on net sales of ALPN-101. In exchange, AbbVie receives an option to an exclusive license for ALPN-101. During the option period, Alpine will conduct all future clinical development, manufacturing and commercialization activities for ALPN-101.
What is ALPN’s background?
Founded in 2015 to develop immunotherapy treatments based on the development of recombinant, protein-based therapeutic solutions, the venture was launched in Seattle, Washington. Co-founders of ALPN include Mitchell Gold, CEO (formerly with Dendreon), Ryan Swanson, and Michael Kornacker. Interestingly, it would appear two of the founders are not employed by the venture anymore. According to Crunchbase, they raised at least $49.3 million in venture capital from Frazier Healthcare Partners and Alpine Bioventures as well as OrbiMed. In 2017, they acquired Nivalis Therapeutics. Based on a LinkedIn review, they employ about 50.
What is ALPN’s core strategy in the market?
They first and foremost have sought to drive their lead candidate program ALPN-101 through clinical development for the treatment of inflammatory diseases. By executing this deal with AbbVie they have successfully structured a path forward to accomplish this while securing a decent payment in the process. Additionally, they seek to aggressively progress other pipeline investigational products, such as ALPN-202.
What is their pipeline?
In addition to ALPN-101 (which is targeted at AGVHD, Lupus and Rheumatoid Arthritis), their ALPN-202 targeting oncology (advanced malignancies) is in a Phase I clinical trial. A product focus on Engineered Cellular Therapies is still a preclinical activity. ALPN-202 represents their oncology program focusing on a conditional CD28 costimulatory and dual checkpoint inhibitor intended for the treatment of cancer. Early stage data (preclinical) reveals potential monotherapy efficacy in tumor models superior to approved therapies. Hence, they opened up NEON-1, a Phase I dose escalation and expansion study in patients with advanced malignancies. They are seeking to enroll payments in 2020 and 2021.
Who are ALPN’s competitors?
For ALPN-101, AbbVie/ALPN will face competitors targeting either ICOS or CD28 (or one of their ligands). They note in their annual 10-K disclosure to the SEC that to their knowledge they have no competitors with a single molecule targeting ICOS and CD28 simultaneously. They do note that Amgen (rozibafusp alfa (AMG570/MEDI0700) an anti-BAFF, anti ICOSL bispecific antibody, would be considered competitive. Additionally, ImmunoTherapeutics SA is developing (FR104) is an anti-CD28 monoclonal antibody fragment. Finally, AtoxBio, Inc. (reltecimod [AB-103]), an anti-CD28 peptide, could be considered in some way competitive to ALPN-101. Partnering with AbbVie helps the small biotech’s cause now.
As far as competition in the class that ALPN-202 falls in, there are literally hundreds of clinical trials for immuno-oncology products used as a single agent or in combination. ALPN suggests that one of the novel attributes of their approach is that it combines inhibitory receptor antagonism and activating constimulation with a single molecule interacting with multiple immune targets.
The immuno-oncology space is competitive and they list several other competitors for both APLN-202 as well as for their “Novel Platform.”
As far as their Novel Platform, considered a multifunctional therapeutic protein platform some of the more dangerous competitors include the following:
· Amgen (BiTE®): fusion proteins consisting of two single-chain variable fragments to link T-cells to tumors.
· Macrogenics Inc. (DART®): Dual-Affinity Re-Targeting and Trident technology platforms bind multiple targets with single molecule.
· Xencore Inc. (XmAb Bispecific): Optimized Fc domains for improved potency, half-life and stability.
· Regeneron, Inc.: VEGF Trap and VelociSuite® antibody technology platforms.
· Five Prime Therapeutics, Inc: proprietary protein library and rapid protein production and testing platform.
Like most small biotech, they burn through funds. In just the last two years, ALPN has lost $78.7 million, according to their 10-K disclosure. At $12.10 per share, their market capitalization equals $224.9 million as of this writing. The company went public via a reverse merger with its acquisition of Nirvalis in 2017.