Lori Lyons-Williams, Neumora president and chief operating officer

After years of biopharmas tiptoeing away, neuroscience is enjoying renewed interest and development activity from both giants and startups. Last summer, Takeda and PeptiDream expanded a central nervous system collaboration launched in late 2020 to potentially more than $3.5 billion, while GlaxoSmithKline joined Alector to launch an up to $2.2 billion partnership focused on the notoriously difficult indications of Parkinson’s and Alzheimer’s diseases.

Also taking aim at neuro drug development is Neumora Therapeutics, which has formally launched with $500 million in hand. Of that, $100 million consists of an equity investment from Amgen, which is partnering with Neumora to develop new precision therapies for diseases originating in the brain. The remaining $400 million is a Series A financing led by ARCH Venture Partners, which founded Neumora in 2019 and operated the company in stealth mode until emerging in early October.

Neumora contends that it can do for neuroscience what more than a decade of R&D has done for oncology, namely bring to market precision therapies targeting neuropsychiatric disorders and neurodegenerative diseases stemming from disorders of the brain.

“If I’m diagnosed with major depressive disorder and you’re diagnosed with major depressive disorder (MDD), right now, the way that happens is that there’s this constellation of nine symptoms. You can have any five of them and still be diagnosed with MDD. But we can have very different underlying biology that’s actually driving the complexities of that condition,” Lori Lyons-Williams, Neumora’s president and chief operating officer, told GEN Edge.

“One of the reasons the company has been founded, and founded now, is because we haven’t understood these drivers so well—and frankly, because you can’t easily take a biopsy of the brain,” Lyons-Williams added.

Neumora relies on a scalable precision data science platform designed to identify and define patient subtypes by mapping the mechanisms that drive brain diseases, using multiple open-source and proprietary datasets collected by Neumora across neuropsychiatric disorders and neurodegenerative diseases.

The company’s proprietary toolbox of neural network technologies integrates multiple types of data across genomics, imaging, electroencephalogram (EEG), digital and clinical domains to create Data Biopsy Signatures™ designed to map underlying disease mechanisms to Precision Phenotypes™ that identify distinct patient subtypes.

That approach, Neumora says, enables it to match the right patient populations to targeted therapeutics, thus de-risking clinical trials and increasing the odds of improved patient outcomes.

Triangulating on a phenotype

“No one of those elements, those unique model data representations, is going to be powerful enough to really identify a more homogeneous population. It’s really the integration of these multimodal data elements that is going to allow us to really triangulate in on a precision phenotype,” said John Dunlop, PhD, Neumora’s chief scientific officer.

John Dunlop, PhD, Neumora chief scientific officer

“On the data science side, we have much more advanced neural net analytics, multivariate auto encoder type technologies, available now that allow us to really integrate and analyze that multimodal data in ways that we couldn’t do before,” Dunlop added.

“We’ve not only focused on clinical data but we focus on preclinical and discovery data because that’s the way that you bridge back to anchor a targeted subpopulation to a molecular mechanism that you predict is going to respond better in that subpopulation. That’s the overall approach that we are doing leveraging the platform.”

While in stealth mode, Neumora began assembling its pipeline of eight treatment candidates. Two are in clinical phases: Lead candidate NMRA-140, a kappa opioid receptor (KOR) antagonist in development for major depressive disorder (MDD) and anhedonia, is in Phase IIa, while NMRA-511, a vasopressin 1A receptor (V1aR) antagonist for anxiety disorders, is in Phase I.

NMRA-140 and -511 joined Neumora’s pipeline when the company acquired BlackThorn Therapeutics, a 2013 spinout of Scripps Research focused on neurobehavioral health.

BlackThorn is one of four companies Neumora has acquired since its stealth launch. The others are:

  • Boston-based Abelian Therapeutics, a drug developer focused on harnessing and investigating glial cells as factors in brain disease;
  • Alairion (Cambridge MA), a startup focused on discovering and developing novel treatments for sleep disorders and sleep-related comorbidity; and
  •  Syllable Life Sciences (Cambridge MA), a machine learning-focused developer of data models designed to understand behavior and help drug developers treat neurological conditions.

Four of Neumora’s pipeline prospects are preclinical candidates developed in house:

  • NMRA-094, a pre-IND candidate for sleep disorders designed to work as a dual antagonist of both H1 and serotonin 5-HT2a (5HT2a) receptor systems.
  • NMRA-NLRP3, a discovery-phase, NLRP3-targeting neurodegenerative disease candidate.
  • NMRA-GRIN2A and NMRA-GRIN2A, both discovery phase neuropsychiatric disorder candidates targeting GRIN2A and GRIN2B, respectively.

The H1 and serotonin 5-HT2a (5HT2a) receptor systems, Dunlop said, are two of the most important brain arousal systems intimately associated with sleep quality and architecture.

“We’ve also brought in with the acquisition a very deep phenotyping platform for actually measuring sleep parameters using polysomnography,” Dunlop said. “Sleep is one of the most highly translatable things that you can measure between preclinical species and clinical species so that also allows us to go into phase one program where we already have a targeted precision phenotype that we can study. So we can actually even get an early signal of clinical efficacy, even in Phase I.”

Neumora expects NMRA-094 will be its next IND candidate and enter the clinic next year—possibly to be joined by additional pipeline candidates.

Probably across 2022 and 2023, we expect that will advance another probably four to six INDs and so we will be getting into the clinic with a number of these programs,” Lyons-Williams said.

Connecting with Amgen

Through its collaboration with Amgen, Neumora acquired exclusive global rights to develop and commercialize two additional pipeline candidates for neurodegenerative diseases that are now in discovery phases—one targeting casein kinase 1 delta (CK1δ), renamed NMRA-CK1δ; and the other targeting glucocerebrosidase (GCase), renamed NMRA-GCase.

Dunlop oversaw both candidates while at Amgen, where he led the neuroscience research program responsible for therapeutic discovery activities in neurodegenerative diseases, pain and migraine, before joining Neumora last year.

The licensing rights to candidates and the $100-million equity investment were two of three elements to the Amgen-Neumora collaboration. The companies will also apply Neumora’s platform to insights in brain diseases that are generated by Amgen’s deCODE genetics subsidiary in addition to human data research capabilities. deCODE is a global pioneer in discovering key genetic risk factors for dozens of diseases acquired by Amgen in 2012 for $415 million.

“That’s a genetic capability that’s unique to Amgen. It’s world class, and we believe will help us supplement our platform in ways that are likely to lead to new target discovery,” Lyons-Williams said.

Neumora reasons that the candidates it is licensing from Amgen have potential beyond their present indications. Dunlop noted that GCase is one of the strongest genetic risk factors for Parkinson’s disease but it’s also been associated with that Gaucher disease, whose cause has been attributed to low levels of GCase.

As for CK1δ, Dunlop said, molecules have been identified that had shown “really great potency and selectivity for the target, really good brain penetration and already evidence of central target engagement and pharmacodynamic activity.”

“Our thinking there is that we could really move that program very quickly if we were able to bring it into the portfolio,” Dunlop added.

Amgen and Neumora said their collaboration aimed to “discover unique and unprecedented insights into brain diseases across neuropsychiatric and neurodegenerative diseases, including schizophrenia and amyotrophic lateral sclerosis (ALS)”—two neuro diseases where drug development has mostly resulted in failed candidates.

“As we had built the capabilities around the platform, and already knew that we had this in house discovery capability in our own lab, we wanted to also jumpstart the company and say, ‘Where can we actually apply the insights from our own platform to programs that are already further along in development?’ ” Lyons-Williams said.

“Strategically we looked for assets that we felt could uniquely benefit from this platform approach from the precision approach. We found those so that we could have opportunities to prove out our platform, prove out our theory with things that were further along in development, and then allow also the earlier-stage discovery programs to catch up, if you will,” she added. “What that will mean for us, overall, is that we will take a lot of good learnings from these first couple of clinical programs.”

With its equity investment, Amgen took an undisclosed ownership stake in Neumora, but no exclusive right to acquire the company in the future. “If we ever got to the point where something like that was happening, then it would be open for other parties as well,” Lyons-Williams said.

Fulfilling 2019 commitment

For Amgen, the Neumora collaboration fulfills a commitment it made when it jettisoned most of its in-house neuroscience pipeline in 2019 by ending its neuro research and early development programs, except for programs centered on neuro-inflammation.

During Amgen’s Q3 2019 earnings call, David W. Meline, then the company’s chief financial officer, told analysts: “We are exploring other models to capitalize on our genetics capability and advance our broader efforts in neuroscience, and we’ll provide guidance on those activities in the future.” [Meline joined Moderna as CFO last year].

Neumora’s workforce has grown to 90 employees, divided between the company’s Boston-area headquarters in Watertown, MA, where it has set up its own wet lab and bases its data sciences team; and the San Francisco Bay Area, where many corporate functions are based

“Obviously, both those markets are rich with talent for exactly the type of work that we want to do, so we do anticipate that we will continue to grow over the next couple of years,” Lyons-Williams said. “We would expect most of the growth to be on the data sciences side, as well as kind of the clinical and translational medicine side, because as we get these programs advancing hopefully through the clinic, we’ll need to kind-of scale appropriately to be able to support those.”

Lyons-Williams and Dunlop are part of Neumora’s executive team, which is headed by Paul L. Berns, the company’s co-founder, chairman and CEO. Other executives include Mike Poole, MD, co-founder and advisor; Carol Suh, co-founder and vice president, business development;  Josh Pinto, PhD, chief financial officer; Tamara Tompkins, JD, general counsel; John Reynders, PhD, chief data sciences officer; Jane Tiller, MBChB, FRCPsych, chief medical officer; Nick Brandon, PhD, chief research officer; Bill Aurora, PharmD, chief external affairs officer; Julie Person, chief people officer; and Lori Houle, senior vice president, quality.

In addition to Berns, Neumora’s board includes two managing directors with ARCH who co-founded the company, Kristina Burow and Robert Nelsen, a co-founder of the VC firm. Also on the board are Matthew K. Fust, former executive vice president and chief financial officer, Onyx Pharmaceuticals; Maykin Ho, PhD, retired partner, Goldman Sachs Group and a veteran life sciences industry executive; and Stacie Weninger, PhD, founding board member, Neumora and president, F-Prime Biomedical Research Initiative, an affiliate of F‑Prime Capital.

The company has also named members of its Scientific Advisory Board and Technology Advisory Board, including scientific co-founders Morgan Sheng, MD, PhD, co-director of the Stanley Center for Psychiatric Research at the Broad Institute; and Richard Huganir, PhD, professor of neuroscience at the Johns Hopkins University School of Medicine.

Joining ARCH Venture Partners in the Series A financing were Alexandria Venture Investments, Altitude Life Science Ventures, Catalio Capital Management, F-Prime Capital, Invus, Logos Capital, Mubadala Capital, Newpath Partners, Polaris Partners, re.Mind Capital (Apeiron), Softbank Vision Fund 2, Surveyor Capital (a Citadel company), Waycross Ventures (Byers Capital), and other undisclosed investors.

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