A glimpse at data for just 11 patients was enough to convince Ultragenyx Pharmaceutical that GeneTx Biotherapeutics is worth $75 million.
After an interim data drop late Monday afternoon, Ultragenyx is exercising its right to acquire partner GeneTx for $75 million upfront, bringing a drug the two companies have been developing together for the rare neurogenetic disorder Angelman syndrome fully under Ultragenyx's fold. The deal also includes undisclosed future milestone and royalty payments.
Ultragenyx's shares dropped 16% as the market opened Tuesday to $50.72, compared to a prior close of $61.
In 2019, Ultragenyx picked up an option to acquire the small biotech GeneTx and its antisense oligonucleotide GTX-102 for Angelman syndrome. The rare disease causes developmental delay, issues with balance, motor impairment and seizures. Currently, there are no approved therapies for the disease.
GeneTx grew out of The Foundation for Angelman Syndrome Therapeutics (FAST), a patient advocacy group that sourced donations to take the asset through preclinical development. The therapy is designed to inhibit expression of UBE3A-AS, the antisense transcript that regulates the silencing of the gene at the root of Angelman syndrome.
Despite the limited nature of the phase 1/2 data, Ultragenyx President and CEO Emil Kakkis, M.D., Ph.D., saw "encouraging early clinical activity" and no safety issues of concern in the interim analysis. The companies already have a plan to up early loading doses for future testing, a method that has previously been shown to be tolerated by patients, according to the CEO.
The data, along with the science from GTX-102 inventor Scott Dindot, Ph.D., of Texas A&M University, "have given us the confidence to exercise our option to acquire GeneTx at an earlier timepoint," according to Kakkis. Ultrageyx plans to move GTX-102 into late-stage development.
This early buy out also saves Ultragenyx some cash down the line—$20 million to be exact, the company said on a July 18 investor call. In April 2022, the two companies entered an amended purchase agreement that provided the option for a $75 million upfront payment for the acquisition and a $30 million milestone when GTX-102 enters a phase 3 trial. This is compared to the original $125 million purchase agreement should an acquisition take place at the end of 2022.
The acquisition includes exclusive global rights to data and intellectual property related to GTX-102 and other additional antisense oligonucleotides.
Small but meaningful
The interim data comes from the trial’s first 11 patients—nine in the U.K. and Canada and two in the U.S.—showing an improvement in clinical disease and an acceptable safety profile, according to a release.
Physicians involved in the U.S. portion of the trial reported changes in sleep, behavior, communication, gross motor and fine motor skills for patients, suggesting positive clinical activity for GTX-102. The U.K. and Canada groups saw similar changes in disease severity as assessed by a number of scales for toddler development and Angelman severity.
The trial's main goal is safety, with other outcome measures assessing changes in motor function, sleep, behaviors and communication. The study will enroll a total of 20 patients between 4 and 17 years old.
"I am convinced we are seeing evidence of a therapeutic effect with GTX-102 though it's still early in the study,” said primary investigator Erick Sell, M.D., associate professor of Neurology and director of the Angelman clinic at the Children's Hospital of Eastern Ontario.
Another primary investigator, Elizabeth Berry-Kravis, M.D., Ph.D., a professor of pediatrics at the Rush University Medical Center in Chicago, said the changes were small but meaningful, given the patients are severally developmentally impaired, non-verbal and normally have a very slow rate of learning.
In 2020, dosing was paused for the trial after all five U.S. patients receiving GTX-102 experienced extremity weakness, with some patients temporarily losing the ability to walk. Following a dosing amendment, the issues cleared up in the patients, and in January 2022, a data safety monitoring board okayed the dose-escalation phase of the trial.
Now, with the dosing amendment in place, no clinically significant safety issues at doses up to 10 mg were reported. No lower extremity weakness or patterns of increasing inflammation were observed. The most common adverse events seen in the U.K. and Canadian group were vomiting, COVID-19 and transient back pain.
In May, U.K. and Canadian health authorities approved a protocol amendment to the study that allows Ultragenyx to start additional, new cohorts of patients with the higher monthly loading doses. Enrollment has already begun under the changed protocol and the first patient has been dosed in the new cohorts. Loading doses are when a higher amount of a drug is administered at the beginning of treatment, before dropping down to a lower maintenance dose.
Since there haven’t been any further drug-related safety issues observed, Sell believes the therapy’s efficacy could be boosted by increasing monthly loading doses, along with a continued increase to the maintenance part of the protocol.
Redosing for the original patients subject to the pause is set to begin in Canada. Ultragenyx did not provide a timeline for the U.S. portion of the trial getting back on track, but said the amended protocol will be used here pending discussions with the FDA.
The next trial update is slated for late 2022 or early 2023.