Dainippon Lays Out R&D Table Ahead Of Latuda Challenges
Focus On Novel Schizophrenia Candidate
Executive Summary
Vant deal, discovery platforms help Japanese firm build out pipeline before it faces the first expiries for its top seller.
If all goes according to plan, Sumitomo Dainippon Pharma Co. Ltd. (SDP) is planning to have up to 11 compounds nominated for clinical development in both the psychiatry/neurology and oncology areas by the end of next fiscal year.
Rounding out the R&D portfolio in the mid-sized Japanese firm's other strategic focus area will be six projects in regenerative medicine/cell therapy, adding to the 10 candidates being brought into the fold through last year's deal with Roivant Sciences Inc.
Building up the pipeline is critical ahead of the first patent expiries in early 2023 for SDP's current top seller, the atypical antipsychotic Latuda (lurasidone), and was one of the driving forces behind the $3bn acquisition of multiple specialist "vants".
The ultimate longer-term goal, president and CEO Hiroshi Nomura told a recent R&D briefing, is to position the expanded company as a "global specialized player" by 2033.
The most immediate pay-off from the vant deal is the expected US approval of the beta-3 agonist vibegron for overactive bladder, submitted in December. (Also see "Sumitovant Keeping Sumitomo Dainippon-Acquired Roivant Companies On Track" - Scrip, 29 Jan, 2020.)
Other near-term commercialization candidates in fiscal 2020 (starting in April) include lurasidone for schizophrenia and bipolar depression in Japan, dasotraline for binge eating disorder in the US, and apomorphine for "off" episodes in Parkinson's disease in the US, Nomura noted.
Besides acquisitions, SDP has also been taking steps to improve its own in-house R&D efforts, including the fostering of cross-team and -discipline exchange of ideas to adopt common biological or technology approaches that might yield multiple benefits.
This is expected to pay particular dividends in psychiatry/neurology, where chief scientific officer Toru Kimura said the hope is to raise the number of clinical candidates to the new target of 11 from just two in the previous fiscal year.
"Research efficiency has been significantly improved…I feel that productivity has been doubled or tripled," helped by the "Virtual One Team" cross-fertilization initiative, he told the meeting.
SDP has also just made an undisclosed investment in the MPM Oncology Innovations Fund in the US, which invests in academia and start-ups, with a focus on those linked to the Dana-Farber Cancer Institute.
Technology Platforms
It was clear from the meeting that SDP is turning to multiple platforms to help drive pipeline expansion.
The obsessive-compulsive disorder drug DSP-1181 gained attention in late January for the claim that it was the first artificial intelligence-generated drug to enter clinical trials.
The long-acting 5-HT1a agonist was created using UK firm Exscientia Ltd.'s Centaur Chemist platform, which Kimura explained enabled exploratory research to be completed in less than 12 months using AI-led design against a database of G protein-coupled receptor interactions.
Elsewhere, US subsidiary Sunovion Pharmaceuticals Inc.'s use of PsychoGenics Inc.'s SmartCube in vivo phenotypic screening platform has identified several early-stage CNS candidates in Parkinson's disease, depression and Alzheimer's agitation.
Novel Neuropsychiatric Candidate
There was a focus and analyst interest at the briefing on one of these, SEP-363856, a first-in-class molecule that has now moved into the pivotal Phase III DIAMOND suite of four global studies in adult and adolescent schizophrenia.
The TAAR1 (trace amine-associated receptor 1) agonist alters dopamine synthesis and release, rather than binding to D2 or serotonergic (except 5-HT1A) receptors as many current CNS molecules in this space do.
"We believe the TAAR1 system acts at both the VTA [ventral tegmental area] and the dorsal raphe [serotonergic nucleus] to alter dopamine synthesis and release," Sunovion's chief scientific officer Kenneth Koblan said.
The molecule already has US Breakthrough Therapy designation and is seen by the company as having potential for both positive and negative symptoms of schizophrenia, including cognitive impairment, and for hallucinations/delusions in Parkinson's patients.
The safety profile versus existing therapies is improved, with a lack of extrapyramidal symptoms, and no movement disorder symptoms or weight, metabolic impairment issues, Koblan noted.
SEP-363856 met its primary endpoint in an earlier monotherapy trial, showing significant improvement in PANSS total score versus placebo after four weeks.
The first DIAMOND data readouts are expected in fiscal 2021, while results from a Phase II trial in Parkinson's psychosis should come in the 2020 first half.
Other potential mood disorder indications are also being explored, Koblan disclosed, noting that "bipolar depression is a potential indication, as is MDD [major depressive disorder] and adjunct MDD."
Cell Therapy/Oncology
Elsewhere in the focus therapeutic areas, there are plans to resubmit a US Biologics License Application for Enzyvant Sciences Ltd.'s RVT-802, a one-time regenerative cultured thymus tissue therapy for immune reconstitution in pediatric patients with congenital athymia.
Originated by Duke University in the US, the product has US Breakthrough Therapy and orphan status but received a Complete Response Letter last December over manufacturing concerns. (Also see "Keeping Track: US FDA's Rejection Of First RMAT BLA Blemishes Otherwise Positive Week Of Non-Oncology News" - Pink Sheet, 9 Dec, 2019.)
In Japan, there is a plan to use an investigator-initiated, Phase I/II study to support an approval filing for a Parkinson's treatment using allogeneic induced pluripotent stem cell-derived dopaminergic neurone precursor cells.
Three of the seven patients in the study have already received the cell implant therapy, which has Sakigake (pioneering therapy) status in Japan and for which a launch is currently envisaged in fiscal 2022.
In oncology, the most advanced candidate continues to be the ROS generator napabucasin, which is moving forward in Phase III trials for colorectal cancer despite failing in a same-stage study for pancreatic cancer in July 2019. (Also see "Dainippon’s Lead Boston Asset Hits Wall In Pancreatic Cancer " - Scrip, 4 Jul, 2019.)