A pair of upsized IPOs packed away cash by way of identical terms, with Boston-based Akouos Inc. and Fusion Pharmaceuticals Inc., of Hamilton, Ontario, separately selling 12.5 million shares at $17 each for $212.5 million in gross proceeds.
Gene therapy-focused Akouos, which develops drugs for hearing disorders, increased the number of shares from 8.33 million and boosted the price from a range of $14 to $16. The deal is expected to close on or about June 30. The company granted underwriters an option for a period of 30 days to buy as many as about 1.8 million more shares. Bofa Securities, Cowen and Piper Sandler are acting as joint book-running managers for the offering, with BTIG serving as lead manager. Akouos, the name of which means “listen” in Greek, came out of the IPO gate loud, closing (NASDAQ:AKUS) at $22, up $5, or 34%.
In SEC paperwork related to the IPO filing, Akouos said it has generated promising preclinical data with lead candidate AK-OTOF for hearing loss due to OTOF gene mutations. OTOF encodes otoferlin, a protein that enables the sensory cells of the ear to release neurotransmitter vesicles in response to stimulation by sound to activate auditory neurons. The company wants to restore otoferlin expression through targeted delivery of its AAVAnc80, containing the OTOF gene, and selected AAVAnc80 from the larger AAVAnc vector library based on its high observed transduction efficiency in inner hair cells. Affected individuals are typically born deaf, which is confirmed through Auditory Brainstem Response (ABR) testing. “Based on feedback from the FDA, we are designing our phase I/II trial to include ABR as an efficacy endpoint,” which should “enable us to quickly determine a clinical response, and potentially result in rapid advancement towards a pivotal trial.” An IND submission is due next year, with first data to come in 2022.
Though starting with indications that involve mutations in a single gene, Akouos intends to build toward gene therapies for the most common forms of hearing loss, including age-related and noise-induced. The most advanced pipeline programs address “a range of inner ear cells and leverage different modalities,” the company said, including CLRN-1 for Usher type 3A, an autosomal recessive disorder characterized by progressive loss of both hearing and vision; GJB-2 for a common form of monogenic deafness and hearing loss; and an anti-VEGF therapy for vestibular schwannoma, a tumor of the auditory vestibular nerve. As of March 30, the company had about $120.1 million in cash and cash equivalents.
Akouos faces plenty of well-partnered competition. Among players in the space is Decibel Therapeutics Inc., of Cambridge, Mass., with efforts in hearing and balance disorders. Decibel's lead candidate is being investigated for the prevention of ototoxicity associated with cisplatin chemotherapy, but the firm has also disclosed a potential gene therapy for OTOF congenital deafness. In 2017, Decibel said it would include one of its product candidates in the collaboration with Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc.
Also in the mix is Frequency Therapeutics Inc., of Woburn, Mass., with small-molecule therapeutics to selectively activate progenitor cells. Frequency's phase II lead program is focused on regenerating hair cells through activation of progenitor cells for sensorineural hearing loss. In 2019, the company made public a partnership with Tokyo-based Astellas Pharma Inc. under which Astellas agreed to oversee development and commercialization of its lead program worldwide, except the U.S., where Frequency assumes those responsibilities.
San Diego-based Otonomy Inc. and Applied Genetic Technologies Corp., of Gainesville, Fla., have sealed a pact meant to co-develop and co-commercialize an AAV-based gene therapy, still at the preclinical stage, in order to restore hearing in individuals with sensorineural hearing loss caused by a mutation in the GJB-2 gene. Sensorion SA, of Montpellier, France, is busy with would-be therapies for inner ear disorders, and has formed a collaboration with Institut Pasteur in gene therapy programs targeting hearing loss. The company’s early gene therapy programs target Usher syndrome type I and OTOF deficiency.
Fusion boosts offering, too
Working on next-generation radiopharmaceuticals, Fusion in its IPO granted underwriters the same option as Akouos, with the same closing date. Fusion, too, went above its predicted $14 to $16 range, and hiked the number of shares sold from 8.4 million. Morgan Stanley, Jefferies, and Cowen are acting as joint book-running managers for the offering, with Wedbush Pacgrow serving as lead manager.
Fusion has developed the Targeted Alpha Therapies, or TAT, platform as well as Fast-Clear linker technology so that researchers could connect alpha particle-emitting isotopes to antibodies and other targeting molecules in order to selectively deliver the alpha particle payloads to tumors. Lead candidate FPI-1434 uses Fast-Clear to hook a humanized monoclonal antibody that targets the insulin-like growth factor 1 receptor (IGF-1R) to the alpha-emitting isotope actinium-225. IGF-1R is a “well-established tumor target that is found on numerous types of cancer cells, but historical attempts to suppress tumors by inhibiting the IGF-1R signaling pathway have been unsuccessful in the clinic,” the company noted in its S-1 filing. A phase I trial of FPI-1434 as a monotherapy in patients with solid tumors expressing IGF-1R is underway, with first data from the dose-escalation portion due about three to six months after Fusion fully resumes clinical activities hobbled by COVID-19. Also undergoing study is the combination potential of FPI-1434 with checkpoint inhibitors, as well DNA damage response inhibitors such as those in the poly ADP-ribose polymerase class. An earlier-stage candidate, FPI-1966, eventually will be the subject of an IND for the treatment of head and neck and bladder cancers expressing fibroblast growth factor receptor 3. That will happen about six to 12 months after the company gets up to speed again preclinically, Fusion said. Incubated in the Centre for Probe Development and Commercialization at McMaster University and launched in February 2017, the company had $67.4 million in cash as of March 31 and in June banked $62.5 million of gross proceeds in connection with an additional closing of its class B preferred share financing. Shares (NASDAQ:FUSN) closed flat at $17.