J.P. Morgan Notebook Day 4: CRISPR's Not Worried; Theratechnologies' HIV Niche; And Is Moderna's IPO Coming Soon?
Executive Summary
Daily round-up of news and notes from the 2018 J.P. Morgan Healthcare Conference: Alder's Options for CGRP drug; CRISPR's not worried about Cas9 controversy; Theratechnologies seeks more HIV niche products; Moderna is shaping up to have a big 2018; TG Therapeutics and Immunomedics milestones ahead.
Alder Keeps Its Commercial Options Open In Migraine
Alder BioPharmaceuticals Inc. was talking to potential partners at J.P. Morgan for its calcitonin gene-related peptide (CGRP) drug eptinezumab, which has shown promising efficacy in Phase III clinical trials. The company released positive Phase III data on the migraine treatment during the conference, which ran Jan. 8-11 in San Francisco, showing 15% of patients treated with the drug experienced a 100% response for three months following a single intravenous infusion; 61% achieved a 50% reduction in migraine days or greater from baseline.
The company is still awaiting some additional data readouts from the four studies that make up the clinical program for eptinezumab but Alder expects to be on track to file the drug with the US FDA in the second half of 2018.
The question is how Alder might commercialize eptinezumab if and when it is approved. The company has no commercial-stage products and would be going up against some deep pocketed rivals in what is expected to be an intensely competitive space. Amgen Inc./Novartis AG and Teva Pharmaceutical Industries Ltd. are in a tight race to be first to market with their respective CGRP drugs, which are both dosed subcutaneously monthly. Eptinezumab is dosed every intravenously every three months.
"We remain pretty confident in our ability to independently execute," Chief Business Officer Mark Litton said. "That said, we are always looking for opportunities that will add value and will accelerate the commercial side." The company is considering potential partners in the US and globally.
CEO Randall Schatzman noted deals outside the US could be particularly attractive, since the company doesn't have any expectations to build out in Asia or Europe. Alder reached an intellectual property settlement with Teva related to the CGRP antibodies, which clears the way for the drug's launch (Also see "Deal Watch: As J.P. Morgan Waits For New Deals, Sanofi Takes Care Of Old Business" - Scrip, 9 Jan, 2018.)
More J.P. Morgan Coverage
For other news from the first three days of the conference, see these stories:
Reflections From J.P. Morgan: Challenges As Always And Reasons For Optimism
J.P. Morgan Notebook Day 3: Lilly's CGRP Prospects, Juno On Track, Color From Alnylam's Greene, Shire's New CMO
J.P. Morgan Notebook Day 2: Walmsley On Diversity, Amgen's Overseas Cash, Growing Opdivo, Mylan On US Generic Pricing, Boston's Pipeline And J&J In Alzheimer's
China Looms Large Seeking New Funding, Deals At J.P. Morgan
J.P. Morgan Notebook Day 1: Tax Reform At Last, Allergan's Job Cuts, Teva Turnaround, Biogen's Cash, And Getting FDA-Friendly
Celgene's $1.1bn Impact Buy Is First Of More Deals To Come In 2018 And Beyond
Deal Watch: As J.P. Morgan Waits For New Deals, Sanofi Takes Care Of Old Business
Pharma Justifies Steep Prices, Plans Fancy Footwork In The Era Of Cures
Shire May Split Up – But Punting On Bigger Decisions For Now
Pfizer Exits Early Neuroscience, But M&A Could Allow Later Re-Entry
CRISPR Therapeutics Unfazed By Cas9 Controversy
A new paper released on the Friday before the J.P. Morgan conference suggested the potential for high levels of resistance to gene-editing medicines, but CRISPR Therapeutics AG CEO Sam Kulkarni said that will not be a problem for the company's lead development program.
That's good news for CRISPR, which is preparing to be the first company to take a CRISPR/Cas9-based gene-editing therapy into the clinic. CRISPR's stock fell 2.8% after the paper authored by Carsten Charlesworth, et. al. from the Department of Pediatrics at Stanford University was published in the online preprint archive bioRxiv, which is operated by Cold Spring Harbor Laboratory. However, the share prices of other CRISPR specialists Editas Medicine Inc. and Intellia Therapeutics Inc. fell 10.6% and 11.8%, respectively, on Jan. 8 based on the bioRxiv preprint.
Because the Cas9 protein in CRISPR/Cas9 technology often is derived from the common bacteria Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes), the authors looked at donor cells in an attempt to understand how much of the population may be resistant to Cas9-containing therapies. The researchers found antibodies against S. Aureus Cas9 (SaCas9) in 79% of the donor cells and antibodies against S. pyogenes (SpCas9) in 65% of the cells. There were no antigen-specific T-cells against SpCas9, but 46% of donors has T-cells against SaCas9.
However, CRISPR Therapeutics is developing its lead product candidate as an ex vivo therapy, meaning that cells are withdrawn from the patient, edited in culture, then delivered back to the patient.
"For ex vivo, I think [Cas9 resistance] is irrelevant," Kulkarni said in an interview with Scrip. "The Cas9 goes in to edit, then it gets chewed up before the cells go back in to the patient."
For in vivo therapies, where a drug is administered to the patient and cells are edited inside the body, he said Cas9 resistance may only be an issue when the therapy is designed to continually edit DNA rather than perform a one-time edit.
CRISPR's partner Vertex Pharmaceuticals Inc. apparently is not concerned about Cas9 resistance in patients treated with the gene-editing firm's technology, because Vertex had a 90-day period to opt in to the development of CTX001 in beta-thalassemia and sickle cell disease, but it waited only 10 days to flag its interest, according to Kulkarni. (Also see "CRISPR Therapeutics President Sam Kulkarni On Business Development" - Scrip, 18 Aug, 2017.)
CTX001 involves engineering hematopoietic stem cells so that they produce high levels of oxygen-carrying fetal hemoglobin in red blood cells, which may alleviate transfusion-dependence in beta-thalassemia and reduce acute pain crises in sickle cell disease. The therapy has performed as designed in healthy donor and patient cells in preclinical studies, increasing fetal hemoglobin to levels that correspond with transfusion independence or a reduction in sickled cells.
CRISPR filed a clinical trial application (CTA) with the European Medicines Agency in December and will file an investigational new drug (IND) application with the US FDA in the first half of 2018 so that the company can start a Phase I/II clinical trial for CTX001 in beta-thalassemia this year. If data from the first 12 patients enrolled is encouraging, the trial will be expanded and serve as a pivotal study to support approval.
Theratechnologies Seeks Niche HIV Drugs
Canadian biopharma firm Theratechnologies Inc. could have US FDA approval for its monoclonal antibody Trogarzo (ibalizumab) prior its April 3 user fee date, but the company is already looking ahead to what it could market alongside the treatment for multi-drug resistant (MDR) HIV-1.
Scrip spoke with Theratechnologies President and CEO Luc Tanguay and Senior Vice President and Chief Financial Officer Philippe Dubuc during the J.P. Morgan conference about the company's appetite for drugs serving subpopulations overlooked by the broader HIV market's major players.
The market for Trogarzo, which has shown impressive efficacy in patients who no longer respond to conventional oral HIV therapies, is estimated to be about 20,000 to 25,000 patients in the US. (Also see "Confidence Builds For Theratechnologies' Game-Changing HIV Monoclonal" - Scrip, 5 Oct, 2017.) The CD4-directed therapy was licensed from TaiMed Biologics Inc. in March 2016 for $2m up front.
Trogarzo's original user fee date was Jan. 3, but that was extended to April 3 when the FDA requested additional chemistry, manufacturing and controls (CMC) information in late November. However, Theratechnologies believes approval could happen before April based on its ongoing dialog with the agency, Dubuc said.
The company has grown its small US sales force to about 70 representatives, who currently detail Egrifta (tesamorelin) for lipodystrophy in patients with HIV. Egrifta reaches an even smaller market than Trogarzo and its 2017 sales are expected to total about C$42m to C$45m.
"Having a commercial organization already in that field, to find another [niche product in HIV] makes sense," Tanguay said, noting that Trogarzo will hit the market as Theratechnologies prepares to lose patent exclusivity for Egrifta. The company also has rights to Trogarzo in Europe and other select countries, and it is expected to reach the market in the EU about 18 months after the US launch, he said.
"At this point, we are looking at HIV only and we're looking at patients who are left behind," Tanguay said. Products of interest may be commercial, but too small for a larger company to justify a significant marketing spend, or assets may be acquired from smaller firms with a candidate that could help Theratechnologies build out its research and development pipeline.
"Our sales force now could probably sell three or four products," Dubuc said. "There are not that many commercial products in HIV [for sale,] but there are some good products in development. There are some unmet needs in HIV."
2018 Could Be A Big Year For Moderna
Moderna Therapeutics LLC continues to present at J.P. Morgan to keep investors interested, but the company still hasn't revealed when it will go public. CEO Stephane Bancel previously has said Moderna won't pursue an initial public offering until it has clinical data from multiple messenger RNA (mRNA) therapeutics – a strategy the private company can afford, because it's raised more than $2bn to date in venture capital, partnership fees and grants, and it had $910m in cash as of Dec. 31.
However, the time for an IPO may be coming soon, since Moderna now has 10 mRNA therapeutics in the clinic and disclosed during the J.P. Morgan meeting that of nine more candidates, at least three are expected to move into human studies in 2018. President Stephen Hoge told Scrip in an interview during the conference that clinical trials have been completed for three of the company's first 10 product candidates, but only one – for a flu vaccine – has been published to date.
However, clinical data from more programs will be revealed this year, including results for a vaccine candidate that should be published soon. While partner AstraZeneca PLC has not disclosed results from its Phase I study for the companies' heart failure program, the big pharma deemed the program successful enough to merit a Phase II study, which Hogue said AstraZeneca will initiate within the next few weeks. (Also see "AZ Makes Fresh mRNA Move With Ethris Respiratory Pact" - Scrip, 21 Aug, 2017.)
Moderna's internal pipeline is focused on infectious diseases, immuno-oncology and rare liver diseases, but it is working with several partners in those and other therapeutic areas, including AstraZeneca PLC and Merck & Co. Inc. The company views its partnership with Vertex Pharmaceuticals Inc. "as a window into pulmonary" that can help Moderna determine whether it should develop its own mRNA medicines in that therapeutic area. (Also see "Moderna Signs Single Drug Deal With CF Expert Vertex For Up To $315m" - Scrip, 7 Jul, 2016.)
While the company has been slow to reveal specifics around its closely-watched mRNA therapeutics, Moderna has moved its programs forward quickly. Hoge noted that the company's first IND application was filed 25 months ago and now 10 programs are in the clinic with some moving into Phase II. "The next couple of years are the proving point," he said.
The company was built and funded on the idea that mRNA therapeutics should be judged based on the results of multiple programs rather than a single drug, so that Moderna's whole platform isn't tossed aside based on a single failure. "We could easily have done one drug at a time; that was never the vision the company was trying to accomplish," Hoge said.
With the kind of money and attention Moderna has attracted while maintaining a relatively slow drip of preclinical and clinical data, the company has a lot of critics, which its president describes as healthy in a science-based industry. (Also see "Biopharma Unicorn Moderna Highlights Secretive Pipeline As Investors Await IPO" - Scrip, 16 Jan, 2017.)
"Our ambition to do this is so disruptive, it's viewed skeptically," Hoge said. "We think it will work broadly. We have to go prove it, not just for the skeptics, but for ourselves."
TG's Expectations
TG Therapeutics Inc. is set to release top-line data in the first quarter from a Phase II study of its UNITY-CLL study of its ublituximab (G-1101), which has been bioengineered to target CD20, in chronic lymphocytic leukemia (CLL) and updated Phase II results in multiple sclerosis. (Also see "TG Celebrates High Risk CLL Data - But Cloud Looms From Rival Trial" - Scrip, 9 Mar, 2017.)
The company noted that the it expects to see a 15% improvement for ublituximab in combination with its PI3 kinase inhibitor umbralisib (GR-1202) over Roche's next-generation anti-CD20 antibody Gazyva (obinutuzumab) plus chlorambucil, and an objective response rate ranging from 84% to 88% in treatment-naïve and relapsed/refractory (RR) CLL patients.
"If all goes as planned, the company aims to file for an accelerated approval in front-line and RR CLL in Q4 2018, however management was uncertain of when it could provide a mature PFS endpoint for full approval, citing 2019 as a possible time point when an adequate number of PFS events would be reached. The company gave no indication what their strategy would be if the estimated endpoint targets were not met," Biomedtracker analysts noted.
Immunomedics Looks Forward To Launch
Immunomedics Inc. is looking forward to a first quarter FDA filing of the antibody-drug conjugate sacituzumab govitecan, which it hopes will get accelerated approval in metastatic breast cancer (mTNBC); the firm is mulling over a European filing.
The Phase III ASCENT study is enrolling patients and positive results from a single-arm, open-label Phase I/II study in mTNBC were reviewed at the conference.
Recently, Immunomedics announced a $250m deal with Royalty Pharmato fund operations through 2020.
That will provide sufficient cash to fund operations until 2020, enabling Immunomedics to prepare the drug for commercialization in mTNBC, and to further development in urothelial cancer, the company noted.
[Editor's note: The J.P. Morgan Notebook is a shared effort for Scrip and Pink Sheet readers, part of our joint coverage of key industry events.]