NEW YORK – The 40th Annual JP Morgan Healthcare Conference is being held virtually this week due to the ongoing coronavirus pandemic. Day three continued to be busy for firms operating in the precision oncology drug and testing markets. Our coverage of presentations from day one and day two can be found here and here.
Below are brief reports on presentations webcast by the companies or through the JP Morgan conference portal on Wednesday.
Iovance interim CEO Fred Vogt said the firm is on track to submit its much-anticipated biologics license application with the US Food and Drug Administration for lifileucel for advanced melanoma during the first half of this year.
A Phase II trial, data from which the company presented at the 2021 American Society of Clinical Oncology's annual meeting last year, showed a 36 percent objective response after a median of 33 months follow-up among previously treated, advanced melanoma patients on the autologous tumor infiltrating lymphocyte, or TIL, therapy. According to Vogt, the responses have deepened over time, and the response rates represent a significant improvement over what this patient population would otherwise face after progression on a PD-1 checkpoint inhibitor or BRAF/MEK inhibitor.
Despite these promising clinical trial results, Iovance has faced challenges validating a potency assay to demonstrate lifileucel's consistency and clearing it with the FDA. The firm has been telling investors that its BLA filing is just around the corner since 2019, but the submission has been repeatedly delayed.
Vogt assured that in the past year, Iovance "worked very hard" to get the agency's feedback on its application, resolve outstanding issues with its potency assay, "and prepare for our BLA submission in the first half of 2022." When pressed for more details on Iovance's interactions with the FDA, he responded that "it's a very detailed process with a lot of steps, and we really don't want to be out there talking about each individual [FDA] meeting."
He told investors, however, that the feedback from the agency has been positive and that the FDA has given tangible advice about what it needs to see from Iovance to be comfortable that the company can "detect and release potent lots and screen out sub-potent lots."
In recent years, the FDA has struggled to set standards for potency assays in the autologous cell therapy space. However, if the agency accepts the lifileucel potency assay, it will help guide other biotechs looking to commercialize these highly bespoke treatments.
Acting on its confidence that TIL commercialization is nigh, Iovance spent much of the past year getting its ducks in a row for lifileucel's launch, building a 136,000-square foot cell manufacturing facility, and identifying an initial 40 authorized treatment centers across the country for initial patient treatment. Iovance expects to treat about 1,000 patients with lifileucel per year.
Iovance is also in talks with the FDA about potentially including data from a Phase II cervical cancer trial in the pending lifileucel BLA and is continuing to enroll a Phase II study of non-small cell lung cancer patients treated with therapy, which Vogt said could be registrational, depending on the agency's feedback.
Beyond its internal TIL programs, Iovance is also developing genetically modified autologous TILs through a collaboration with Cellectis. The companies are planning to submit an investigational new drug application with the FDA and begin clinical trials this year for a modified TIL product, IOV-4001, which is engineered to inactivate PD-1. Vogt did not disclose which tumor types the company will study this TIL in.
Iovance's board of directors is actively searching for a new full-time CEO, but Vogt said there were no updates to share at this time.
Elevation Oncology is expecting data readouts this year from a Phase II study of its lead precision oncology candidate seribantumab and is eyeing opportunities to expand its pipeline through internal development and licensing deals, CEO Shawn Leland said.
Last June, New York-based Elevation partnered with Caris Life Sciences to identify oncogenic fusions and mutations that the testing company had identified in patients via whole-exome and transcriptome sequencing, in the hopes of using this data to discover therapeutic opportunities and prioritize its pipeline.
This year, Elevation will continue working with Caris to inform its drug development. Leland noted that Caris' data showing the prevalence of a mutation in different tumor types allows his team to make a business case for potential new targets. The company did not highlight any new targets that it has identified through the partnership yet.
"We're looking to identify assets that may be available for in-licensing or companies for acquisition that would allow us to focus on developing programs and accelerating drug development, analogous to what we've done with seribantumab in NRG1 gene fusions, as well as launching novel drug discovery campaigns as we build out our research capabilities," Leland said.
In mid-2022, Elevation expects to report initial data from a small cohort of patients from its CRESTONE study, a Phase II trial of seribantumab in patients with advanced solid tumors harboring an NRG1 gene fusion, no other actionable mutations, and who have not previously received a pan-ERBB, HER2, or HER3 targeted therapy. The early results are expected to include data from 10 patients, Leland said. He also expects to complete enrollment in the first cohort of the study, totaling 20 patients.
The CRESTONE trial also includes two exploratory cohorts with patients who have received prior pan-ERBB, HER2, or HER3 targeted therapy and with patients who have NRG1 fusion with other actionable mutations.
Although, initially, Elevation is exploring seribantumab in the relapsed or refractory setting, the company believes the drug can potentially benefit patients in earlier treatment settings.
"We hope to maximize the value of seribantumab, by not only catering to the relapsed or refractory patient with NRG1 fusions, but potentially expanding into earlier lines in patients with NRG1 fusions as well as expanding into other genomically defined patient populations, potentially patients with HER3 overexpressed and amplified cancers," Leland said.
The company is also beginning to consider regulatory approval pathways for seribantumab. One scenario, Leland explained, is pursuing breakthrough therapy designation for seribantumab in NRG1 fusion-positive solid tumors from the US Food and Drug Administration. Once the CRESTONE trial completes initial enrollment this year and yields results, Elevation may also begin exploring accelerated approval pathways with the agency, Leland said.
Autolus Therapeutics CEO Christian Itin shared updates on its autologous CAR T-cell therapy pipeline, including on its lead candidate obecabtagene autoleucel (obe-cel), which it is developing for acute lymphoblastic leukemia and B-cell malignancies.
During the second half of this year, the London-based firm expects to share complete remission rate data from its Phase II FELIX trial investigating obe-cel as a treatment for ALL, and in early 2023, Itin said the firm should report data on key secondary endpoints like event-free survival and duration of response.
The firm is also evaluating AUTO1/22, a version of obe-cel that also targets CD22 in addition to CD19, for pediatric ALL patients, and the firm expects to share data from that trial during the first half of this year.
Compared to already approved autologous CAR T-cell therapies for leukemia and lymphoma, such as Gilead's brexucabtagene autoleucel (Tecartus), Autolus believes its therapy will have an improved toxicity profile because the cells are designed to avoid a high degree of overstimulation, which can cause toxicities like cytokine release syndrome. Across three separate Phase I studies that the firm has already conducted evaluating obe-cel in a total of 50 patients, none of the patients experienced high-grade cytokine release syndrome.
The obe-cell CAR T cells were also reliably persistent in these early studies, Itin said. In one of these studies, called ALLCAR19, after a median follow-up of 29.3 months, the event-free survival rate was 46 percent among adult ALL patients on obe-cel.
Beyond obe-cel and AUTO1/22, Autolus is also developing CAR T-cell therapies for T-cell lymphomas, including AUTO4, which is currently in a Phase I clinical trial for patients with relapsed or refractory T-cell lymphoma whose tumors are TRBC1 positive. Itin said the firm expects to share interim data from this trial during the first half of this year. Autolus also plans to begin two additional Phase I clinical trials for autologous cell therapies, AUTO8 and AUTO6NG, for multiple myeloma and neuroblastoma patients respectively, during the first half of this year.
At the end of 2021, Autolus announced that Blackstone Life Sciences had committed to investing up to $250 million to support obe-cel's development in adult ALL. Itin said this gives Autolus a strong opportunity to build up commercial manufacturing capacity and advance the FELIX trial.
Black Diamond Therapeutics
Black Diamond Therapeutics CEO David Epstein discussed two MasterKey EGFR inhibitors under development, BDTX-189 and BDTX-1535, and a MasterKey BRAF inhibitor program. The Cambridge, Massachusetts-based firm is studying BDTX-189 in a Phase I/II trial for EGFR- and HER2-mutated solid cancers, including non-small cell lung and breast cancers.
In the dose escalation phase of the study, the firm will enroll patients with allosteric HER2 or HER3 mutations, EGFR or HER2 exon 20 insertion mutations, EGFR exon 19 deletion or L858R mutations, or HER2 amplified or overexpressing tumors. In the Phase II portion, the trial will include patients with allosteric HER2 mutations, including S310F/Y, R678Q, L755S/P, V777L, V842I, and others, as well as patients with EGFR or HER2 exon 20 insertion mutations.
So far, Epstein said, BDTX-189 has demonstrated antitumor activity in patients with EGFR exon 20 insertion mutations and HER2-amplified tumors and has been well tolerated with no dose-limiting toxicities observed. The firm will report on safety data and provide updates on this trial throughout 2022.
Black Diamond was also cleared by the US Food and Drug Administration this week to begin a Phase I clinical trial of BDTX-1535, its MasterKey EGFR inhibitor for biomarker-selected glioblastoma and NSCLC patients. The trial, which Black Diamond will begin during the first quarter of 2022, will include a cohort of glioblastoma patients with EGFR alterations known to be associated with the disease; a cohort of NSCLC patients with intrinsic resistance mutations in EGFR exon 18; and a cohort of NSCLC patients with acquired resistance mutations.
The drugmaker expects to report data from this first-in-human trial during the second half of 2023. Epstein said the firm will report out any updates in the meantime, too.
Unlike earlier EGFR inhibitors that target specific types of EGFR mutations, using the MasterKey approach, Black Diamond's drugs can block a "family of mutations," which in the case of EGFR, includes canonical, non-canonical, and drug-resistance mutations. Historically, EGFR-mutated glioblastoma patients haven't benefited from first generation EGFR inhibitors, Epstein explained, which is why Black Diamond decided to study its brain-penetrant drug in this setting.
Black Diamond is also on track to initiate IND-enabling studies for its BRAF inhibitor MasterKey program this year and hopes to have an FGFR inhibitor drug candidate selected in late 2022.
Biomea Fusion plans to begin clinical studies of its lead candidate, the menin inhibitor BMF-219, in seven tumor types in 2022. The Redwood City, California-based company has already begun enrolling patients in a Phase I trial of the drug in relapsed or refractory acute myeloid leukemia and acute lymphocytic leukemia, including patients with an MLL or KM2TA gene rearrangement or NPM1 mutation.
In the first half of 2022, Biomea plans to begin another Phase I trial in diffuse large B-cell lymphoma with mutations in MYC, BCL2, and BCL6, also called double/triple hit lymphoma and double expressor lymphoma; and in MYC-driven multiple myeloma, said CEO Thomas Butler.
In the second half of 2022, the company expects to file an investigational new drug application and begin a subsequent Phase I study of BMF-219 in KRAS-mutant colorectal, pancreatic, and non-small cell lung cancer.
"Last year was really a breakout year for Biomea Fusion; we started the year with seven employees having just completed a Series A raise," Butler said. "Fast forward through the year, we went through the IPO process and raised $150 million that really allowed us to build out the infrastructure of our R&D engine to fully explore BMF-219."
With BMF-219 moving into the clinic, Biomea also plans to announce its next development candidate in oncology in the first half of 2022 and has a third oncology candidate also on the horizon. As of Q3 2021, the company has $192 million in cash, cash equivalents, and investments.
Helen Sabzevari, CEO of Precigen, said the company will continue advancing studies of its UltraCAR-T therapies in ovarian cancer, blood cancers, and ROR1-positive cancers, and will begin discussions with the US Food and Drug Administration about its HPV-targeted immunotherapy candidate.
In 2022, Precigen expects to initiate a Phase II trial of its HPV vaccine PRGN-2009 and a checkpoint inhibitor in advanced HPV-associated cancers. The Phase I study of PRGN-2009 in combination with Merck KGaA's anti-PD1 drug, M7824, showed a response rate of 40 percent in early results. Sabzevari noted that the company is seeking the FDA's input on the regulatory path it should take for PRGN-2009 in HPV-associated cancers.
"We will be initiating a Phase II study in advanced HPV patients in combination with anti-PD1 because this is the way that we can move these assets to the frontline, into the standard of care," she said. "In the best scenario, 15 to 18 percent of these patients are responsive to Keytruda. If we can increase that [with the PRGN-2009 combination], this becomes a standard of care and our preliminary data points to that."
Precigen, based in Germantown, Maryland, is also advancing its portfolio of CAR T-cell therapies in the coming year, including PRGN-3006, PRGN-3005, and PRGN-3007. In 2022, the company will begin dosing patients in the Phase I study of PRGN-3007 in ROR1-positive solid tumors and blood cancers. The initial enrollment group will include patients with ROR1-positive chronic lymphocytic leukemia, mantle cell leukemia, acute lymphoblastic leukemia, and diffuse large B-cell lymphoma, along with ROR1-positive triple-negative breast cancer, lung cancer, and pancreatic cancer.
"This is the first umbrella trial [where] we are treating all these various indications under the same trial," Sabzevari said. "ROR1 has become a popular target for many of our competitors, and obviously here we have the edge as we started working on this years ago and we have gotten … [PRGN-3007] in the clinic."
The company will also begin the dose expansion portion of a Phase I trial of its PRGN-3006 CAR T-cell therapy in relapsed or refractory acute myeloid leukemia this year, and it expects to report additional Phase I/Ib data from this study later this year. The company will also expand a Phase I study of its PRGN-3005 CAR T-cell therapy in ovarian cancer and initiate a multicenter expansion phase.
CEO Kevin Conroy said Exact Sciences has tested 7.5 million people with Cologuard and 1.5 million with Oncotype Dx.
The firm saw 18 percent year-over-year revenue growth in 2021, with a 30 percent jump in screening and 27 percent increase in precision oncology testing, as described in the firm's pre-announced FY21 earnings.
"We expect to achieve $2 billion in revenue this year, and we expect Cologuard to be a major contributor to growth," Conroy said. Furthermore, the firm expects to be profitable by 2024 through a leadership position in colorectal cancer screening, multi-cancer early detection, and minimal residual disease recurrence and monitoring with a total addressable market of $60 billion.
Exact will release data on Cologuard 2.0 at the ASCO Gastrointestinal Cancers Symposium next week. The test can improve the false positive rate and pre-cancer detection of Cologuard through the use of different biomarkers, Conroy said. The firm's forthcoming colon cancer blood test will be made available through the current screening platform and noted that internal case-control data exceeds Medicare requirements.
The firm plans to bring together methylation, mutation, protein, and other markers to improve upon multi-cancer early detection technologies. "We are the only ones taking this approach, and this combination through two major studies we are doing this year will lock down our test and allow us to move into a clinical trial and make our test available as a lab-developed test prior to FDA approval," Conroy said.
In the precision oncology business, which includes Oncotype Dx and Oncotype Map brands, Conroy said 98 percent of US oncologists have ordered the tests, which have been evaluated in more than 300 publications.
Exact is also gathering case-control data for minimal residual disease recurrence tests that are tumor-informed and tumor-naïve. Within the MRD space, Conroy said Exact Sciences is set apart from competitors like Natera by its commercial organization. "This is a huge opportunity, we're a company that can help answer these questions, and large health systems are telling us, 'We don't want to work with 20 different providers,'" Conroy said.
Conroy noted that recently acquired PreventionGenetics will help the firm launch its germline hereditary disease test. "They have whole-genome sequencing expertise, a team of 15 Ph.D. geneticists who help deliver great results for patients, and relationships with 300 health systems," Conroy said. The hereditary disease test will be deployed across every salesperson in the organization, he also said.
Conroy suggested that the market for hereditary cancer testing is "only minimally penetrated with the great work that Invitae and Myriad have done," adding, "We intend to expand the market, not take away share — our ability to call on 260,000 primary care physicians in all the large health systems in the US changes everything."