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Small Molecule Highlights #21 – February 2024

Small Molecule Highlights #21 – February 2024

In this issue of “Small Molecule Highlights” we bring you 5 new small molecules out of recent drug discovery journals. These molecules target a diverse selection of targets, including BRAF, ATR, SARS-CoV-2 3C-like protease, ADAMTS7, and LPAR1. Enjoy!


KIN-2787 (Exarafenib)
KIN-2787 (Exarafenib)

KIN-2787: Paradoxical activation of RAF dimers (homo- and hetero-) continues to be a confounding issue in the development of specific RAF inhibitors as a monotherapy.  While advances have been made in pan-RAF inhibitors that can block dimer-dependant signaling, the current state of the art (i.e. naporafenib and belvarefenib) are marred by poor physicochemical properties, namely, solubility.  The team at Kinnate Biopharma looked to remedy this by optimizing the naporafenib scaffold to increase its solubility and circumvent compound metabolism.  Towards this end, the medicinal chemists investigated different alcohol containing appendages to increase solubility.  Incorporation of the chiral alaninol substituent was hypothesized to disrupt crystal packing thereby aiding solubility, as well as protect the solvent exposed alcohol group from oxidative metabolism.  The pyrrolidine urea group was deployed to stabilize the DFG out conformation, with the pyrrolidine group and its pendant trifluoromethyl substituent making key lipophilic interactions within the DFG vacated back pocket.  The morpholino-substituent was maintained from naporafenib as it bestowed the requisite kinase selectivity.  In cellular efficacy studies, KIN-2787 was shown to potently inhibit phosphorylation of ERK in monomeric class I altered cell lines (A375 EC50 = 62 nM and Colo800 EC50 = 103 nM), dimer-driven class II altered cell lines (NCI-H2405 EC50 = 10 nM, BxPC-3 EC50 = 51 nM, and OV-90 EC50 = 26 nM) and heterodimer class III altered cell lines (WM3629 EC50 = 9 nM, and CAL-12T EC50 = 18 nM).  Crucially, relatively potent pERK inhibition was observed in a standard cell model of drug-induced paradoxical activation (IPC-298 cells; EC50 = 265 nM).  Kinase selectivity was assessed across a panel of wild-type and mutant kinases (Reaction Biology; 688 kinases in total), with only DDR (both wild-type and mutant) showing up as significant off-target kinases.  The compound demonstrated good hepatocyte stability across species (% remaining @ 60 min = 85/72/69/62 in human/rat/dog/mouse) and respectable oral bioavailability in rat, mouse and dog (F(%) = 44/82/96 in mouse/rat/dog).  Pharmacodynamic evaluation of KIN-2787 took place in xenograft models exemplifying class I (A375), class II (BxPC-3), and class III (WM3629) NRAS driven cancers where BRAF in mutated.  In all cases, dose-dependant tumor growth inhibition, and regression at the highest doses tested, was observed with no overt signs of toxicity.  Efficacy was also demonstrated in NRAS driven models harboring BRAF WT protein (SK-MEL-2 in NOD SCID mice).  Given the excellent PD data, a phase I dose escalation trial (NCT04913285) was conducted to examine plasma exposure and appropriate dosing (300 mg/kg BID gave an average plasma concentration of 250 nM).  A follow-up safety and efficacy study in patients with BRAF and/or NRAS mutant positive solid tumors is currently recruiting (NCT04913285). 

Reference: https://doi.org/10.1021/acs.jmedchem.3c01830

RP-3500 (Camonsertib)

RP-3500 (Camonsertib)
RP-3500 (Camonsertib)

RP-3500 (Camonsertib):  This latest report from the team at Repare Therapeutics provides a very nice example of pharmacophore driven drug optimization.  The target, ataxia telangiectasia and Rad3-related (ATR) kinase, is a key protein in multiple DNA-damage response pathways, offers opportunities for synthetic lethality with several proteins, including ATM and BRCA1/2.  Taking AZ20 (AstraZeneca) as a starting point, the medicinal chemistry team quickly evaluated requirements for efficient binding and selectivity towards ATR.  Their assessment revealed a key hydrogen bond donor interaction requiring the pyrazole of RP-3500, and a need for structural rigidification of the original AZ20 scaffold to orient this substituent correctly (via azaindazole ring).  A further breakthrough in SAR was realized with the identification of the tertiary alcohol group which provided desirable physicochemical properties and increased metabolic stability.   These modifications bolstered potency (HeLa IC50 = 0.9 nM) and bestowed exquisite selectivity for ATR (i.e. 30-fold selectivity over mTOR demonstrated in LoVo cells).  Pharmacokinetic characterization of RP-3500 revealed acceptable to good oral bioavailability across species (F(%) = 72/45/113/56 in mouse/rat/dog/monkey) with rat exhibiting the highest clearance of all the species tested.  Unfortunately, erythroid cell toxicity is a commonly encountered issue observed with ATR inhibitors in vivo.  To minimize the impact of anemia in live subjects, RP-3500 was subject to a variety of dosing regimes to deconvolute the kinetics of erythroblast depletion/recovery in response to the compound.  Intermittent dosing schedules (i.e. 3 days on/4 days off) were found to be the most effective.  Furthermore, the authors showed that coadministration of RP-3500 with PARP inhibitors (Niraparib) concurrently on an intermittent dosing schedule could effectively control tumor growth in Granta-519 tumor-bearing mice without severely impacting the erythroid cellular compartment.  With a number of active and recruiting clinical trials in play, Camosertinib looks to ameliorate the dose-limiting toxicities that beleaguered previous ATR inhibitors.   

Reference: https://doi.org/10.1021/acs.jmedchem.3c01917



CMX990:  Leveraging its drug repurposing library ReFRAME (Repurposing, Focused Rescue, and Accelerated Medchem), medicinal chemists at Calibr found numerous starting points that could be quickly pushed to active antivirals at the height of the COVID pandemic.  A number of initial hits were found to target SARS-CoV-2 3C-like protease (CLpro); a protein responsible for the processing/cleavage of virally encoded polyproteins.  As a starting point, a peptidomimetic compound developed by Pfizer (PF-00835231) was selected and its structure optimized to increase efficacy and decrease clearance.  The first major advance in the SAR was incorporation of the trifluoromethoxymethyl ketone as the cysteine engaging warhead substituent.  This group provided a 3-fold increase in potency and improved in vitro (human liver microsome) by > 30-fold.  Tethering of the middle portion of the compound via proline further enhanced the pharmacokinetic properties of the compound, leading to enhanced oral exposure.  Characterization of CMX990 in cells revealed potent activity in HeLa cell models of SARS-CoV-2 alpha, delta, and omicron infection (63 nM, 35 nM, and 37 nM, respectively).  ADMET analysis confirmed lower clearance in human liver hepatocytes and microsomes compared to Nirmatrelvir (> 3-fold improvement) and no observed hERG liabilities (IC50 > 10 μM) or CYP inhibition (IC50 > 45 μM across 5 major cytochromes).  Measures of genotoxicity (i.e. Ames and MNT tests) were also negative.   In pharmacokinetic studies, CMX990 exhibited tractable to good oral bioavailability in all species tested other than monkey (F(%) = 14.5/12.2/52.8/1.1 in mouse/rat/dog/monkey).  Follow up MTD studies in CD-1 mice and beagle revealed no sustained adverse effects, even at doses of 1000 mg/kg/day for 5-days.  Remarkably, CMX990 was progressed to a Phase I clinical trial in only 10 months after its synthesis, however, no further clinical development has been disclosed.  Taken as a whole, CMX990 is a sobering reminder of the need to develop pharmaceuticals against targets without a human homolog.

Reference: https://doi.org/10.1021/acs.jmedchem.3c01938



BAY-9835:  Matrix metalloprotease ADAMTS7 has been implicated it the development and progression of coronary artery disease (CAD).  Multiple genome-wide association studies, as well as knockout and catalytic domain loss of function studies, have made ADAMTS7 an intriguing target for therapeutic intervention.  However, selectivity across the 19-member zinc metalloprotease family has historically been difficult to attain.  The medicinal chemists at Bayer took an in silico design approach, looking for tractable differences between the catalytic domains of ADAMTS7 and other related metalloproteases to tease apart tractable pockets that could be leveraged for selectivity.  The scientist used a known ADAMTS4/5/7 inhibitor (Eli Lilly; https://doi.org/10.1021/acs.jmedchem.7b00650) as a jump off point and gradually tuned its selectivity through iterative rounds of SAR.  One of the most impactful design decisions was the incorporation of ortho-biphenyl carboxamide to bolster selectivity for ADAMTS7 over the closely related MMP12.  Judicious placement of fluorine on this substituent helped fix metabolic soft spots and contributed to the overall bioavailability of the compound.  Additionally, the methyl pyrazole moiety provided a good trade-off between potency, selectivity, and pharmacokinetic properties.  In vitro, BAY-9835 exhibited activity against ADAMTS7 (IC50 = 6 nM) and exquisite selectivity in a panel of related metalloproteases (1121x/1654x/375x/5467x/962x/17316x selectivity against ADAMTS4/ ADAMTS5/ADAM8/ADAM10/ADAM17/MMP2).  Lower selectivity was observed for ADAMTS12 (5x).  The authors hinted at further work aimed at improving selectivity by modifying the methyl pyrazole substituent, leveraging a potential steric clash with Phe354 of ADAMTS12.  Pharmacokinetic characterization of the compound revealed low blood clearance (CLblood (L/kg/h) = 1.1/0.55/0.02 in mouse/rat/dog) and great bioavailability (F(%) = 100/96/77 in mouse/rat/dog) across species.  In toxicity studies, no inhibition of cardiac ion channels (hERG, hNav1.5, hCav1.2) was observed below 10 μM, and tests for genotoxicity (Ames and MNT) were negative.   In vivo, BAY-9835 was well tolerated in a two-week chronic dosing study in rats (50 mg/kg/day, p.o.) with no observable signs of toxicity. In summation, BAY-9835 possesses desirable activity and selectivity, along with tractable pharmacokinetic properties, which set it apart as one of the first orally bioavailable and selective molecules targeting ADAMTS7.

Reference: https://doi.org/10.1021/acs.jmedchem.3c02036



ACT-1016-0707: Idorsia Pharmaceuticals recently disclosed their lead optimization of an LPAR1 receptor antagonist aimed at overcoming the poor PK of their antecedent molecule(s) (compound 3).  More specifically, low unbound fraction and high clearance in rat made PK and dose predictions in humans untenable.  Towards this end, the medicinal chemistry team looked at reducing the lipophilicity of the original scaffold to find the optimal balance of efficacy and in vivo PK.  Contraction of the central piperidine ring to an azetidine offered tractable gains in solubility and metabolic stability.  Also, dispersing polarity across the molecule (i.e introduction of the chloropyridine) had a similar effect.  Finally, replacing the succinic acid group with a sulfamide circumvented transport via organo anion trasporters (OATP) and ameliorated enterohepatic recirculation issues observed in close congeners. In Tango EDG2-bla U2OS, ACT-1016-0707 exhibited potent and selective inhibition of the LPAR1 (IC50 = 2.9 nM; corrected for unbound fraction, IC50 >10 μM in LPAR2 and LPAR3 reporter cell lines).  ADME and PK characterization revealed low clearance in hepatocytes (CLHep (μL/min/106 cells) = 7.4/n.d./<2 in rat/mouse/dog) and oral absorption (F(%) = 49/79/52 in rat/mouse/dog) warranting further evaluation in vivo.  An LPA-induced skin vascular leakage mouse model was used to assess PD.  In the model, ACT-1016-0707 was shown to significantly reduce vascular leakage at a dose of 30 mg/kg.  Follow up toxicity tests (Ames and Eurofins Panlab safety screen) didn’t flag any substantial genotoxicity of promiscuity issues.  In scope, the structural evolution of preclinical candidate ACT-1016-0707 nicely highlights the design considerations needed to arrive at a compound with a balanced ADMET, PK and efficacy profile.        

Reference: https://doi.org/10.1021/acs.jmedchem.3c01827

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Taleb Sedighi, PhD

Director of Proteomics and Protein MS

Taleb is a distinguished scholar with a PhD in Bioanalytical Chemistry from Simon Fraser University in Canada, complemented by an MSc and BSc in Analytical Chemistry. With a robust 16 years of experience, Taleb’s expertise lies in utilizing mass spectrometry techniques for the analysis of proteins and small molecules.

Since joining Dalriada in January 2021, Taleb has led the development of innovative platforms in chemoproteomics and covalent hit identification cascade, which have significantly contributed to over 20 covalent and targeted protein degradation programs.

Before joining Dalriada, Taleb was a Research Associate at the Patrick Gunning lab at the University of Toronto, where he played a pivotal role in establishing various proteomics and DMPK methods crucial for supporting early drug discovery programs.

Beyond his professional accomplishments, Taleb’s passion for science and research is evident, underscored by his authorship of 46 publications and numerous contributions to patent filings and grant proposals.

Pegah Ghiabi, PhD

Associate Director, Protein Production

Pegah brings over 25 years of extensive experience in biomedical research and leadership, Pegah brings a wealth of expertise in cancer research, protein science, and drug discovery within academic settings.

Prior to joining Dalriada, Pegah served as a senior research associate and Head of the protein production core facility at the Structural Genomics Consortium (SGC), University of Toronto. In this role, she provided strategic guidance and supervision for generating protein targets crucial to numerous drug discovery projects, collaborating with both academic and industry partners. Notable collaborations included projects with Nurix Therapeutics, Pfizer, Bristol Myers Squibb, Takeda, Merck KGaA, Janssen, Novartis, and X-Chem.

As a leader of the protein production team, Pegah brings unparalleled expertise in human and viral protein production. Her proficiencies span target selection, construct design, expression vector selection, protein expression across bacterial, insect, and mammalian systems, protein purification, and biophysical approaches for protein quality assessment. Pegah boasts extensive experience across various target classes, including helicases, proteases, methyltransferases, exonucleases, E3 ligases, polymerases, the WDR protein family, and structural proteins in both human and viruses.

Pegah holds an MSc in Cell Biology from McGill University, Canada, and a PhD in Cellular and Molecular Biology from the University of Paris-Sud (XI), France. After her doctoral studies, she undertook a postdoctoral position at Weill Cornell University in the USA.

Chris Yarnold, PhD

Director, Discovery Chemistry

Chris brings over 20 years’ industrial integrated discovery, medicinal chemistry and project leadership experience.

Prior to joining Dalriada, Chris spent 20+ years at Evotec (UK) as Group Leader in Medicinal/Discovery Chemistry where he was Project Leader for drug discovery projects covering a broad range of Therapeutic Areas and was Global Medicinal Chemistry contact for Metabolic Diseases.

Chris has experience as Project Leader in major disease areas including Cardiovascular, Oncology, CNS and Metabolic diseases.  Additionally, Chris has led anti-infective, iron overload disease and anti-thrombotic collaborations. His expertise includes hit finding and expansion, Hit-to-Lead and Lead Optimization preclinical phases. Three clinical candidates were identified. FV-100 has reached PhIII for shingles, Vamifeport is progressing through PhIIa for iron overload diseases and ONO-7684 is currently in PhI trials as a novel antithrombotic agent.  He has experience in targeting enzymes, GPCRs and transporters with small molecules. Chris has extensive experience of managing teams, encouraging and developing chemists to reach their full potential.

Chris has a B.Sc (Joint Hons) in Chemistry and Biology and a Ph.D. from King’s College London. Chris gained postdoctoral experience with Professor Walter Szarek at Queen’s University, Kingston, Canada and Professor Chris McGuigan at the Welsh School of Pharmacy, Cardiff.

Kaushik Ghosal, PhD

Head of BD, North America

Kaushik Ghosal is a successful entrepreneur and business development executive with over 15 years of bio-pharma experience in a variety of R&D and BD roles across several verticals in R&D business models, corporate expansion and strategic leadership in drug discovery and early development. Most recently Kaushik was Director of BD at Evotec (NASDAQ: EVO) leading partnered drug discovery and development programs for both stand alone and integrated drug discovery projects for several small and large biotechs, drug development accelerators and large pharma clients. 

​Prior to Evotec, Kaushik was the Director of Business Development at BioMotiv where he was instrumental in launching and leading a portfolio of venture-backed biotechs such as Sujana Bio, Optikira, Koutif Therapeutics. During his tenure, BioMotiv and Harrington project grew into a 360M + global initiative and established strategic partnerships with Takeda, Biogen, Arix Bioscience and Charles River Laboratories. At BioMotiv, Kaushik also founded therapeutic focused start-ups such as BioExcel and Inclera therapeutics to advance academic sourced drug discovery programs, some of which developed into clinical stage assets.

Before BioMotiv, Kaushik was Director of R&D at ReXceptor Inc, a clinical stage biotech company where he led preclinical and clinical development, establishing strategic partnerships with pharmaceutical companies and drug-development accelerators. 

Kaushik received MSc in Biotechnology (Indian Institute of Technology, Bombay), a Ph.D. from Miami University and completed his postdoctoral training in Neuroscience from the Cleveland Clinic. Kaushik has served on various advisory and on the boards of non-profit and for-profit organizations in the healthcare field such as NIH, John Hopkins Technology Ventures, EDI and Case Venture Mentorship Program.

Richard Rathmell, PhD

SVP Discovery Chemistry

Rich is Dalriada’s SVP Discovery Chemistry, responsible for scientific strategy of programs in discovery chemistry and a key contributor to the continuous R&D capability build at Dalriada. He brings 23 years of discovery experience, medicinal chemistry, and project leadership working at Eli Lilly and most recently Evotec, in the UK.  

Before joining Dalriada, Rich was Vice President and Head of a Chemistry Department at Evotec UK, where he held strategic and scientific direction oversight for a portfolio of pain and metabolic disorder programs. He helped to shape the vison and direction of the chemistry group and additionally was a key contributor developing new screening strategies, and designing associated libraries, for early phase projects.

Prior to Evotec, Rich gained exceptional experience in integrated drug discovery with a 20+ year career at Eli Lilly UK. He held the positions of Group Leader and Research Advisor, where he had oversight for the portfolio management of his team. Scientifically, Rich has been involved in 25+ integrated drug discovery programs across neurosciences, pain, and metabolic disorders. His expertise spans all stages of drug discovery, from target identification and validation to Hit-to-Lead and Lead Optimization, culminating in the delivery of 8 clinical candidates, two reaching PhI and one still progressing through PhIIa for Alzheimer’s disease. He is familiar with multiple modalities, from small molecules, protein-protein interactions, protein degradation, protein translation inhibition and peptides. He brings extensive experience with target classes such as GPCRs, enzymes, transporters, and ion channels.

Rich has a B.Sc (Hons) and a Ph.D in Chemistry from the University of Exeter UK, before taking up a postdoctoral position working with the late Sir Jack Baldwin at the University of Oxford.

Adam Davenport

Adam Davenport, PhD

Chief R&D Officer

Adam is Dalriada’s Chief R&D Officer. A seasoned drug hunter and innovator, he brings over 22 years of hands-on life science and partnership organization experience, having contributed to drug candidates and clinical assets through both governance and leadership roles.

Prior to Dalriada, Adam’s outstanding career was spent at Evotec, then Oxford Asymmetry International, which he joined in 2001. There, he gained extensive experience from Hit ID through to IND, across diverse modalities, target classes (GPCRs, ion-channels, PPIs, CNS, kinases, enzymes) and therapeutic areas (pain, inflammation, cognition, metabolic, Women’s Health and respiratory).

As a Project Leader, Adam has progressed multiple projects through Discovery into Clinical evaluation and is lead inventor of P2X3R antagonists Eliapixant and Filopixant, achieving Phase 2a PoCs in Persistent Chronic Cough (PCC), and Bradykinin B1R antagonist Fulimetibant, undergoing a Phase 2a study to treat diabetic neuropathic pain (DNP).

Adam’s promotion to VP Medicinal Chemistry saw him take on scientific and strategic portfolio responsibilities as well as operational duties in Abingdon, UK. Progression through Senior to Executive VP expanded Adam’s leadership and strategic influence on the organisation, where he established and led as Head of Global Molecular Discovery, a multi-modality data-driven Design and Synthesis function based in the UK, FR, IT and US.

Passionate about science and communication, Adam has authored over 55 patents, publications and external presentations and was co-recipient of the Bayer Healthcare Drug Discovery Award for Collaborative Innovation in 2017.

Adam holds a B.Sc. Honours degree in Chemistry and a PhD in Organometallic Chemistry from the University of Leicester, UK.

Frosty Loechel, PhD

SVP Biology

Frosty is Dalriada’s Head of Biology, responsible for the scientific strategy of the discovery program in biology and a key contributor to the continuous evaluation of our scientific capabilities, operations, and infrastructure. He brings 20 years’ academic experience and 25 years working in pharma, biotech, and CROs.

Before joining Dalriada, Frosty gained exceptional experience in discovery programs at Evotec. First as a VP, Metabolic diseases, he built up a large department running iPSC work, in vitro pharmacology, advanced cellular platforms, transcriptomics, imaging, and data science. Then, as SVP, Therapeutic Area Lead and Scientific Director, he led on new collaborative drug discovery agreements with pharma/biotech partners and on the strategy of project portfolio in major multi-target collaborations.

Prior experience includes work at Zealand Pharma, where he focused on peptide drugs for a portfolio of diabetes and obesity projects. His earlier career was spent at Lundbeck, Thermo Fisher, Neurosearch and BioImage, where he gained a strong background in a broad spectrum of scientific areas.

Frosty has been involved in hundreds of drug discovery projects and gained a wealth of experience across multiple areas and therapeutic modalities including CNS and metabolic diseases. His expertise spans all stages of drug discovery, from target identification and validation to Hit-to-Lead and Lead Optimization, and nomination of preclinical candidates. He is familiar with multiple modalities, from small molecules, to peptides, to biologics, and brings extensive experience with target classes such as GPCRs, kinases, transporters, ion channels and proteases.

Frosty has a B.A. in Biochemistry from the University of Kansas, and a Ph.D. from the Faculty of Health Sciences of the University of Copenhagen. He is a Danish citizen and is fluent in English, Danish, and Italian.

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Brian Sequeira

Brian Sequeira

Director, Information Systems, PMO

As Director of Information Systems and PMO, Brian leads the IT, PMO and Procurement functions. With a strong foundation in technology, a successful track record in leading cross functional and multi-disciplinary project management teams, and in-depth experience in purchasing and materials management, Brian is passionate about delivering to and exceeding client expectations through critical thinking, analysis and effective communication. He brings more than 20 years experience in various industries including corporate law, pharmaceuticals, biopharmaceuticals and big data market research.

Brian completed his BSc degree in Computer Science from the University of Toronto and certified as a Project Management trainer with Kepner Tregoe.

Lisa Cline

Lisa Cline

Director, Human Resources​

As the Director of Human Resources (HR), Lisa leads this function at Dalriada. Lisa is recognized as a pragmatic partner, team builder and innovator who brings balance and clarity to HR policies, practices, and procedures.

With more than 25 years in a management capacity, Lisa is known for designing and developing programs, performance improvement measures and policies that help organizations build highly engaged workplaces, boost their bottom line, and defuse workplace issues before they escalate.

She began her HR career at GlaxoSmithKline advancing through increasingly responsible positions and supporting practically every division within the company. Lisa has also operated her own HR consultancy. Since joining Dalriada in 2020, Lisa has established an efficient and engaging HR infrastructure that delivers sustainable organizational and cultural success.

Lisa attained her Certified Human Resources Leader designation, (CHRL) from the University of Toronto.

Harpreet Kaur

Harpreet Kaur, PhD

Director Chemistry & ADME

As Director of R&D Operations, Harpreet leads Dalriada’s Chemistry and ADME functions. Passionate about building highly effective, result-oriented teams, Harpreet is known for her strong rapport with clients and inter-disciplinary colleagues.

Harpreet brings more than 20 years R&D experience in both academic and industry settings. Beginning her career at Dalton Pharma Services as a medicinal chemist, Harpreet has progressed into roles such as chemistry team leader, chemistry manager and associate director for R&D operations. Harpreet brings a broad range of drug development experience in preclinical, clinical, and commercial stages for more than 10 pre-clinical candidates and 2 commercial products. Her experience also includes contract research, process development and analytical method development and validation. She has served as SME for process development and analytical method development during FDA and Health Canada audits.

Harpreet completed her BSc degree in Biological Sciences, MSc and PhD degree in Organic Chemistry from Kurukshetra University, India.

Mohammad Eram

Mohammad Eram, PhD

Director Biology & Biophysics

Mohammad attained his PhD in Biochemistry and Enzymology at the University of Waterloo (Canada) and holds MSc degree in Medical Microbiology and a BSc degree in Cell and Molecular Biology. As the Director of Biology Department at Dalriada, he oversees the work of the cell biology, biochemistry and biophysics and proteomics teams.

Prior to joining Dalriada, Mohammad worked on early stage hit discovery projects at the Structural Genomics Consortium in Toronto, including projects in collaboration with Bayer, Takeda, Eli Lilly, and Merck. His work at SGC focused on biochemical and biophysical methods with applications to high-throughput and fragment-based drug discovery.

With over 17 years in biochemical/biophysical assays and small molecule R&D, Mohammad was involved in programs spanning small molecule inhibitor modalities including allosteric inhibitors, tight binders, targeted covalent therapeutics, and protein degraders. These programs covered a diverse range of protein targets including transcription factors, epigenetic modulators, oxidoreductases, dehydrogenases, kinases, methyl- and acetyltransferases, deacetylases, demethylases, PPI, GPCRs, and transcription regulators.

Jeff O’Meara

Jeff O’Meara, MSc

VP Drug Discovery

As Vice President, Drug Discovery at Dalriada, Jeff is responsible for overseeing all drug discovery activities from target identification to pre-clinical development. Jeff has nearly 30 years of drug discovery experience in hit ID, hit to lead, lead optimization and candidate nomination in projects targeting kinases, protein-protein interactions, protein degraders, covalent inhibitors, proteases and GPCRs in the areas of anti-infectives, oncology, immunomodulation, pain and CNS therapeutics. Prior to Dalriada, Jeff was Head of Research at M4K Pharma where he led a successful multinational open science lead optimization drug discovery project targeting DIPG, a rare childhood cancer.

Previously, Jeff spent 8 years as an integral part of the Ontario Institute for Cancer Research’s Drug Discovery team where he drove hit to lead and lead optimization projects of which two were eventually partnered with pharma in deals totaling > $2B. Jeff also trained for 17 years as a medicinal chemist and project team leader at Boehringer Ingelheim Canada Ltd. where he helped discover several novel antivirals that progressed to clinical trials. He has published more than 50 papers and patents in the fields of medicinal chemistry and drug discovery and in 2010 was the recipient of the American Chemical Society’s TAOC award.

Jeff has an M.Sc. in organic chemistry from University of Ottawa.

Tom Coulter

Tom Coulter, PhD

Head, Drug Discovery Programs and Partnerships

Tom is part of the R&D leadership team, overseeing partnership activities, drug discovery program planning and execution, as well as lifecycle management for current and prospective partners.

Over the past three decades, Tom has held senior roles in European pharma and biotech, including almost 20 years in contract research with Evotec as Senior Vice President, Drug Discovery, and more recently growing and leading Selvita’s integrated drug discovery portfolio.

Tom’s background is in medicinal chemistry, and he has extensive experience in the discovery and delivery of new small molecule and biologic agents targeting enzymes, GPCRs and other cell membrane targets including ion channels and SNARE proteins. He has managed multiple drug discovery programs covering the hit identification, hit to lead, and lead optimization stages of drug discovery, including 15 projects resulting in nomination of preclinical development candidates in the fields of cancer, inflammation, endocrine disease and antivirals. Tom has also contributed to the identification of multiple investigational new drugs. In recent years Tom has driven the identification of commercial opportunities as well as the creation and execution of sophisticated integrated discovery collaborations for clients.

Tom has a BSc (Hons) degree in chemistry from the Queen’s University of Belfast and a PhD in organic chemistry from the University of Leeds under Professor Ron Grigg. After completing his PhD, he joined Jim Thomas’ group at the University of Manchester before starting his industrial career at Organon.

Rav Kumar

Rav Kumar, PhD

Chief Strategy Officer

Dr. Rav Kumar is Chief Strategy Officer at Dalriada. He spent 25 years with GlaxoSmithKline (GSK) in the UK, France and Canada at vice-president level leading pharmaceutical R&D and business development. Key areas of expertise include formulation development, regulatory submissions, manufacturing and GMP audits. He has been involved with development of numerous medicines and vaccines plus many successful business change initiatives.

Most recently, he was Managing Director for Apotex in India (Bangalore and Mumbai), leading over 2,000 professionals in Pharmaceutical R&D, Manufacturing, Quality, Regulatory Affairs & Commercial Services.

Dr. Kumar is passionate about growing Canadian Life Sciences and has been involved with many industry-academic-government collaborations for which he was recognized with the Award for Leadership in in Canadian Pharmaceutical Sciences. He conceived the $150M spinout of GSK’s vaccines R&D to create the Neomed Vaccines and Biologics Centre of Excellence in Montreal. Other contributions include the CIHR Steering Committee for Patient Oriented Research, the Board of CQDM Research Consortium in Quebec and President of the Canadian Society for Pharmaceutical Sciences.

Dr. Kumar also serves as Director of The Centre for Medicinal Chemistry and an Assistant Professor at University of Toronto. He has a Pharmacy Degree and completed a PhD in Novel Drug Delivery at University of Bath in the UK.

Charlie Younger

Charlie Younger, PhD

Chief Operating Officer

Charlie joined Dalriada in 2020 as Chief Operating Officer, bringing over 25 years of pharma/biopharma experience. Charlie has a proven track record of leading organizations through rapid growth and transformations.

Charlie started his career as an Analytical Scientist at Glaxo and has taken on progressive leadership roles in pharma/biopharma. Charlie has worked with leading private and public pharma/biopharma organizations including leadership roles at CROs such as Patheon and Therapure Biopharma. He has also served as COO in both public and private organizations.

Driven by a personal passion to grow R&D in Canada, he has been a contributing member on multiple SR&ED tasks forces and executive roles in training organizations.

More recently, Charlie runs his own professional services business since 2016, helping companies grow and/or streamline operations for start-ups through to $B+ multinationals. He completed an HBSc in Chemistry at Western University (Canada) and a PhD in Organic Chemistry at McMaster University (Canada).

Patrick Gunning

Patrick Gunning, PhD

Co-founder & CSO

Patrick is a Professor of Chemistry at the University of Toronto, Canada Research Chair in Medicinal Chemistry, and Founder and Chief Scientific Director of the Centre for Medicinal Chemistry (UofT). Patrick obtained his PhD at the University of Glasgow in 2005 under the supervision of Profs. Robert Peacock and Andrew C. Benniston, and conducted post-doctoral studies at Yale University with Prof Andrew Hamilton.

Patrick’s research has focused on developing inhibitors of numerous protein classes, including transcription factors, kinases, and epigenetic targets, using novel covalent therapeutics and monovalent protein degraders. Patrick has published ~120 research papers, is a Fellow of the Royal Society of Chemistry, won 20 research awards including Canada’s Top 40 under 40, the 2010 Boehringer Ingelheim Young Investigator Award, the 2012 RSC MedChemComm Emerging Investigator Lectureship by the Royal Society for Chemistry, Rose Winer Levin Lectureship at the Dana-Farber Cancer Institute (2015), and the 2016 Canadian Society for Chemistry’s Bernard Belleau award.

Patrick, the co-founder and CSO of Dalriada Drug Discovery, has founded three other biotech companies with over $34M in funding, including Janpix Inc, now a Centessa Pharmaceuticals’ company, Dunad Therapeutics, and Dalriada Therapeutics.

Diana Kraskouskaya

Diana Kraskouskaya, PhD

Co-founder & CEO

Diana completed Honors BSc Degree in Molecular Biology and PhD in Medicinal Chemistry from the University of Toronto, and is a co-founder of two other biotechs, which have raised > $10 M in VC funding.

During her time in academia and biotech, Diana worked on diverse small molecule programs across protein-protein interactions, epigenetics, GPCRs, covalent inhibitors, and is an inventor on several patents.

As a co-founder and Chief Executive Officer of Dalriada, Diana brings to Dalriada years of leadership and hands-on cross-disciplinary biotech and drug discovery experience spanning areas of company building, scientific & IP program strategy, and operations. ​

Following completion of her PhD, Diana took appointment as a research manager of the Centre for Medicinal Chemistry, where she was involved in multiple drug discovery programs and provided oversight over the build-out of the >$100 M integrated drug discovery infrastructure at the University of Toronto. Diana co-founded and led two other biotechs, Dunad Therapeutics and Dalriada Therapeutics. In this process she recognized the shortcomings of the existing options for outsourcing innovative science, which led to the creation of Dalriada Drug Discovery’s Turn-Key™ Model. With this new model and under Diana’s leadership the company has grown to over 60 people within 3 years. ​

Diana is the recipient of several entrepreneurship awards, including RBC Prize for Innovation & Entrepreneurship and the 2018 MNP Future Leaders awards.

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