Medical Director, Clinical Development

Clinical Development San Diego, California


Description

SITUATION OVERVIEW

  • Public, clinical stage biotech with potential for first-in-class mechanism in multiple indications
  • Lead asset in Ph I studies for inflammatory bowel disease; several additional programs in preclinical
  • First precision medicine approach to GI therapeutics, with companion diagnostics for our therapies
  • Global exclusive license to Cedars-Sinai’s GI biobank (the world’s largest) and bioinformatics platform
  • Fully capitalized with top-tier investors: raised $130mm in Nov 2020; IPO in March raised $190mm

Prometheus Biosciences is the world’s first company using precision medicine and machine learning to provide tailored therapies for GI disease. As we continue to expand our pipeline and build a world-class drug discovery and development organization, we are seeking a Vice President, Immunology to join our growing team.

Prometheus is a publicly-traded biotechnology company pioneering a precision medicine approach to the discovery, development, and commercialization of novel therapeutic and companion diagnostic products for the treatment and diagnosis of inflammatory bowel disease (IBD).

The company's precision medicine platform, Prometheus 360, combines proprietary bioinformatics discovery methods with one of the world's largest gastrointestinal bioinformatics databases to identify novel therapeutic targets and develop therapeutic candidates to engage those targets. Prometheus is a spin out of Cedars-Sinai Medical Center and partners with the hospital system for its biospecimens, clinical data, and bioinformatics.

The company is led by an exceptional management team bringing deep experience in GI and autoimmune therapies. CEO Mark McKenna joined in 2019 to refocus the organization around a precision therapeutics strategy after orchestrating a successful turnaround effort at Salix Pharmaceuticals.

With a lead therapeutic program in Phase 1 studies and a robust emerging pipeline, seeking a highly motivated hands-on physician leader as Medical Director. Reporting to the Chief Medical Officer, the medical director will lead the execution of Prometheus Biosciences’ clinical studies in inflammatory bowel disease and other autoimmune diseases.


CLINICAL AND MARKET CONTEXT

Inflammatory Bowel Disease (IBD) is complex and heterogeneous. A ‘one-size-fits-all’ standardized treatment is ineffective for many patients. In fact, 75% of the 2 million patients in the US who have IBD are refractory to first line biologic therapy. Unfortunately, new therapies in development have not demonstrated improvement in remission rates over approved therapies, and no approved therapies exist to address fibrosis in IBD.

Precision medicine has shown great promise across therapeutic areas as innovative companies are increasingly able to leverage clinical biomarkers and genomic insights combined with advanced computational approaches to tailor therapies to individual patients. This approach has not yet been applied to GI disease, despite the known heterogeneity of this patient population.

Prometheus Biosciences’ mission is to create a new paradigm in patient care. The company’s powerful precision medicines platform leverages proprietary technology to translate complex patient data into precision therapeutics and diagnostics, providing an effective treatment solution for every GI patient.


ABOUT INFLAMMATORY BOWEL DISEASE (IBD)

IBD is a complex disease with many contributing factors, including genetic, environmental and immunologic, and is estimated to affect over 2,000,000 people in the United States and over 5,000,000 people globally.

UC and CD are two of the most common forms of IBD. Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the GI tract that begin most commonly during adolescence and young adulthood. UC involves the innermost lining of the large intestine, and symptoms include abdominal pain and diarrhea, frequently with blood and mucus. CD can affect the entire thickness of the bowel wall and all parts of the GI tract from mouth to anus. CD symptoms include abdominal pain, diarrhea, and other more systemic symptoms such as weight loss, nutritional deficiencies, and fever.

The current standard of care for the treatment of patients with moderate-to-severe IBD is typically anti-inflammatory agents; however, none of these therapies address fibrosis, or scarring, in IBD. Since the approval of the first anti-TNF agent for the treatment of CD in 1998, the availability of JAK inhibitors and newer biological agents, including anti-integrin and anti-IL12/23, has improved the care of moderate-to-severe IBD (JAK inhibitors in UC only).

However, these subsequently approved therapies have generally failed to demonstrate a clinical remission effect size of more than 15% relative to placebo. Moreover, among those patients who do respond to therapy, up to 45% will lose response over time. Current therapies used for the treatment of UC and CD apply a one-size-fits-all approach without regard to biologic variations amongst patients, and substantial unmet need remains.


PROMETHEUS 360 PRECISION MEDICINES PLATFORM

The Prometheus 360™ Precision Medicines Platform is a discovery engine that combines high-density disease data with complex analytics to guide development of novel precision therapeutics and companion diagnostics.

For the past 15 years, Cedars-Sinai has built a highly curated database and biorepository containing more than 200,000 samples linked to extensive longitudinal clinical data from over 20,000 patients – one of the largest collections of GI biospecimens in the world. Samples are subjected to ‘big data’-style profiling including genetics, serologics, transcriptomics and microbiomics, to uncover unprecedented insights about immunological networks that drive GI disease.

Utilizing state-of-the-art data mining and machine-learning analysis approaches, Prometheus re-stratifies complex GI diseases into biologically homogeneous subgroups to discover novel druggable targets with unique biomarkers. The company then develops targeted therapeutic options that offer superior efficacy to patients and an accelerated path to the market. In parallel, they design companion diagnostic tests to predict response to these new therapies, ensuring the right drug for the right patient.

Because the platform enables targeted patient selection based on companion diagnostic tests, Prometheus is able to dramatically reduce the cost and time associated with clinical development of new compounds. As the clinical data set continues to grow and machine learning approaches continue to evolve, the platform will only grow more robust over time.


PRECISION THERAPEUTICS & COMPANION DIAGNOSTICS

Prometheus has developed a pipeline of four therapeutic assets in active development. The lead asset PRA023 is a monoclonal antibody against inflammatory cytokine TL1A and has strong potential to be a differentiated market-leading therapy for IBD. This TL1A target is a mediator of both inflammation and fibrosis in IBD and has been clinically validated in human subjects by a 14-week open-label Pfizer study in UC completed in 2019.

PRA023 binds both soluble and membrane-associated human TL1A with high affinity and specificity and has the potential to substantially improve outcomes for moderate-to-severe IBD patients. Prometheus is developing PRA023 for both UC and CD. Discovered at Cedars-Sinai, the asset has been the subject of extensive research and publication over the last 10 years.

In December 2020, the company began a single and multi-dose Phase 1a study of PRA023 in healthy volunteers to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of PRA023. The company plans to follow this study with the first precision medicine trial in GI, a randomized, double-blind, placebo-controlled Phase 1b study of PRA023 in UC and CD patients, with expected data readout in Q2 of 2022.

With the goal of maximizing patient and trial outcomes, the company is developing an associated device, the PRA023 CDx (companion diagnostic) assay. The PRA023 CDx is a genetic-based diagnostic tool designed to identify patients who are predisposed to increased expression of TL1A and are therefore potentially more likely to respond to PRA023. The company intends to evaluate its PRA023 CDx in the Phase 1b clinical trials. The company believes that this novel approach will lead to reduced development costs and timelines, and will ultimately improve patient outcomes.

Additional assets in early development include PR600, an anti-TNFSF mAb; PR300, a GPCR modulator small molecule; and TPR15, a mAb against a novel target in co-development with Takeda.

In 2019, the company announced a collaboration with Takeda for the development of a CDx to complement a drug target in development. In 2020, Prometheus entered into a co-development agreement for our cell signaling Ab program (PR600) and a CDx for IBD.

With the closing of a $130mm Series D financing in November 2020 and a $190mm IPO in March 2021, the company is well-capitalized to complete the development and registrational trials for lead asset PRA023 in UC and CD in 2022, as well as preclinical development and IND filing for PR600.

POSITION SUMMARY

Prometheus Biosciences is seeking a highly motivated hands-on physician leader to serve as Medical Director. Reporting to the Chief Medical Officer, the Executive Medical Director will lead the execution of the company’s clinical studies in inflammatory bowel disease and other autoimmune diseases.

This position will be responsible for the oversight of advancing the clinical studies. S/he will also serve as a medical liaison between investigators and maintain established relationships with key opinion leaders, as well as Health Authorities. The ideal candidate should be trained in internal medicine with subspecialty training in GI, rheumatology, or pulmonary medicine preferred. 

ADDITIONAL RESPONSIBILITIES

  • Provide clinical leadership of trial execution from first-in-human through registrational studies.
  • Contribute to the formulation of study designs, protocol development, in collaboration with cross-functional teams.
  • Provide clinical leadership in the conduct of clinical activities including recruitment, data review, analysis, and reporting that conforms to the highest ethical, safety and quality standards and in compliance with GCP and regulatory standards.
  • Remain current on the therapeutic landscape in the relevant therapeutic areas through review of the scientific literature, interactions with key opinion leaders and other external experts and attendance at relevant scientific meetings, in order to provide input and guidance for the strategic direction of Prometheus Biosciences’ programs.
  • Attend and present at investigator meetings and site initiation visits as applicable.
  • Provide clinical leadership in the preparation of Clinical Study Reports, Annual Reports and other safety reports, Health Authority pre-meeting packages, Investigator Brochures and other periodic clinical reports.
  • Collaborating with cross-functional groups to provide input in publication strategy including active participation in authoring, preparation and review of manuscripts, conference abstracts and presentations and other external presentations of clinical data.
  • Partner with R&D to provide clinical perspective to target selection and development strategy.

EXPERIENCE & QUALIFICATIONS

  • MD degree or equivalent is required.
  • Board Certification or Board Eligibility in internal medicine, subspecialty training in gastroenterology, rheumatology, or pulmonary medicine is highly desirable.
  • 4+ years of experience in clinical research including the design and execution of clinical trials, preferably within a pharmaceutical or biotech environment. Experience in a contract research organization or academic institution is acceptable.
  • Experience with U.S. and European Health Authority interactions and submission of clinical regulatory documents is desirable.
  • Strong written and verbal communication skills; willingness to engage with investigators, key opinion leaders and external advisors; and ability to effectively give presentations at conferences, advisory meetings and other public forums.
  • Willingness to educate and mentor internal and external colleagues and collaborators.

 

PERSONAL ATTRIBUTES

  •  A hands-on, entrepreneurial style with a sense of urgency, a bias toward action, comfort with calculated risk, and the ability to analyze situations rapidly and make prudent decisions
  • Engaged, hands-on, independent and goal-oriented mentality; willingness to work in highly dynamic work environment and embrace uncertainty.
  • Ability to multi-task and willingness to flexibly contribute simultaneously in multiple facets of drug development; willingness to learn new therapeutic areas.
  • Self-motivation; good judgment; strong commitment to follow up on tasks and action items; organizational, analytical, and problem-solving skills; risk identification and management; creative and innovative thinking all highly desirable.
  • Strong ability to work within and lead and motivate a cross-functional matrixed team.
  • The requisite scientific acumen and communication skills to influence and collaborate with key scientific, regulatory, and business leaders.
  • Sound strategic, clinical, technical, operational, and ethical judgment with uncompromising integrity.
  • All qualified applicants are considered for employment without regard to race, color, religion, age, sex, sexual orientation, gender identity, national origin, disability, veteran status or other protected class.


All qualified applicants are considered for employment without regard to race, color, religion, age, sex, sexual orientation, gender identity, national origin, disability, veteran status or other protected class.