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Small Molecule Highlights #23 – March 2024

Small Molecule Highlights #23 – March 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 TRPA1, troponin, EBP, BRD4, and IRAK4. Enjoy!



GDC-6599:  Genentech has recently disclosed their lead optimization of a TRPA1 ion channel agonist for asthma and respiratory inflammatory disease. Their main goal was to mitigate associated anti-coagulation issues found in preclinical monkey models. In the model, repeat dosing of the parent compound was not tolerated, with signs of hemorrhage and blood loss being observed in multiple organs. The pre-clinical conundrum, what could be causing this coagulopathy? The drug development team identified two potential sites of untoward reactivity that might be responsible. The first was an oxadiazolone ring that was prone to ring opening. Such groups are present as covalent warheads for catalytic serine residues in several lipase inhibitors. The solution, deletion of the problematic carbonyl group and rearrangement of the heteroatoms to arrive at the 1,2,4-oxadiazole of GDC-6559. Further optimization of the pendant ether-linked 4-chlorophenyl group was required to dial in the required potency. The second site targeted for optimization was a metabolic soft spot located on the hypoxanthine substituent. Metabolite identification (MetID) in monkey hepatocytes revealed that this group was prone to oxidation. A key piece to the puzzle was found in MetID studies in dog hepatocytes where this metabolite was not observed, implicating aldehyde oxidase (AO) as the main culprit. An AO inhibitor (hydralazine) was added to monkey liver S9 fractions incubated with compound to confirm. Furthermore, the metabolite possessed similar structural features to a group of anticoagulant small molecules targeting VKOR (an enzyme in the vitamin K redox cycle). To mitigate AO mediated oxidation, the researchers surveyed a variety of blocking substituents, finally arriving at a methyl group to prevent formation of the undesired metabolite. In cells, a 4-fold increase in potency compared to the parent compound was achieved after lead optimization (hTRPA1 IC50  = 5.1 nM). GDC-6599 exhibited low clearance in human and moderate clearance in rat hepatocytes (CLHep = 4 and 27 mL/min/kg, respectively). Also, hepatocyte MetID across several species did not detect the problematic metabolite. Pharmacodynamic characterization in a guinea pig model of induced cough revealed dose-dependant inhibition of effect upon application of a TRPA1 agonist (cinnamaldehyde). Follow-up in vivo safety studies did not indicate any signs of significant toxicity in rats or monkey (100 mg/kg, 7-day, chronic dosing). The only finding was a mild prolongation of coagulations with none of the corresponding histological observations observed with the parent compound. The authors attribute this to the ever so slight overlap in structure, especially around the optimized methyl substituent, between GDC-6599 and vitamin K. Currently, GDC-6599 has completed a Phase I clinical trial in healthy volunteers and is currently recruiting for a Phase II study in patients with chronic cough (NCT05660850).

Reference:  https://doi.org/10.1021/acs.jmedchem.3c02121



CK-963:   Scientists at Cytokinetics recently described the development of a novel cardiac troponin agonist for the treatment of physiological conditions related/contributing to heart failure. Specifically, the team was interested in selectively promoting contraction of heart muscle tissues without invoking calcium-dependant pathways. Currently, cardiac calcitrope drugs, such as dobutamine, milrinone, and digoxin, are used to treat acute heart contractility issues. However, significant cardiovascular issues, like cardiac arrythmia and systemic hypotension, have been associated with long-term use, especially with drugs modulating phosphodiesterase-3 (PDE-3). In search of a starting point, researchers screened their internal compound collection for a molecule that sensitizes cardiac troponin to calcium without inhibiting PDE-3. The HTS identified two molecules, one of which exhibited the desired selectivity for cardiac muscles without perturbing calcium homeostasis. SAR around the pyridyl-piperidine substituent was crucial to increasing potency. Modifications to the quinazolinone group were geared towards increasing solubility whilst maintaining selectivity over PDE-3. CK-936 was shown to directly interact with cardiac troponin using isothermal calorimetry (ITC; Ki = 11.5 μM). Sub-micromolar activity was observed in rat derived cardiac myofibrils (AC50 = 0.7 μM). Also, CK-936 was found to be a poor inhibitor of PDE-3 (IC50 > 40 μM). In pharmacokinetic studies, the compound exhibited moderate clearance in rats (CLrat = 7.1 mL/min/kg) and a low plasma half-life (T1/2 = 0.6 h). A pharmacodynamic study conducted in anesthetized rats indicated increased heart contractility upon i.v. administration of CK-963 (cumulative highest dose was 199 mg/kg). In the study, a 40% increase in left ventricle activity was observed at 32.8 μM plasma concentration. Given the underwhelming Phase III results of omecamtiv mecabril (Galactic-HF trial), Cytokinetics has offered a glimpse into the pharmacophores they are exploring next.        

Reference: https://doi.org/10.1021/acs.jmedchem.3c02412

Compound 11

Compound 11
Compound 11

Compound 11:  Multiple Sclerosis (MS) is a debilitating and chronic disease, characterized by progressive decline in cognitive and physical function. The cause, immune-mediated destruction of myelin and myelin-producing oligodendrocytes within the CNS. Recently, the development of “remyelinating” agents has garnered a significant amount of attention as a regenerative medicine approach for the treatment of MS, complementing existing immunomodulatory modalities that do little to halt the progression of the disease. Scientists at Genentech have targeted the emopamil binding protein (EBP) as it plays a role in the regulation of oligodendrocyte precursor cell (OPC) differentiation. A structurally enabled medicinal chemistry program commenced with a cryo-EM structure of an OPC enhancing literature compound bound to EBP. The structure revealed a linear conformation of the compound in the binding pocket, with the piperidine substituent, hypothesized to be protonated in the microenvironment, engaging in crucial long-range H-bonding interactions with  Glu80, Glu122, and Asn193 residues of EBP TM4 (transmembrane 4) domain. SAR around the initial spiroindolinone group successfully dialed in selectivity for EBP and bestowed greater metabolic stability. The hydantoin substituent of compound 11 was found to be the optimal replacement for this group.  Modifications to the pendant aryl group were used to optimize drug half-life. Working within a TPSA range permitting CNS access (<80 Å2), the research team identified the para-cyclopropylphenyl group as the best compromise between lipophilicity and drug clearance parameters. The spiro-piperidine had significant hERG liability concerns as lipophilic basic amines are prevalent hERG inhibitors. Strategies to sterically congest the area around the amine and decrease amine basicity had detrimental effects on activity. In the end, the original tetrahydropyran was maintained as it offered a sufficient therapeutic window (>100-fold). In mouse derived OPCs, compound 11 was found to potently inhibit EBP function (as assessed by EBP substrate accumulation; EC50 = 6 nM). Further studies in human cortical organoid corroborated results found in mouse OPCs (EC50 = 31 nM) and provided substantive support for de novo formation of oligodendrocytes in human cells. Pharmacokinetic evaluation in murine models revealed good oral bioavailability (F(%) = 68/42 in mouse/rat) and BBB penetration (Kp,uu = 0.77/0.74 in mouse/rat; i.v. dosing). In summary, compound 11 provides a therapeutic proof-of-concept to further support the development of remyelination therapies.  It will be interesting to see whether Genentech continues to develop compound 11 as a clinical candidate.           

Reference: https://doi.org/10.1021/acs.jmedchem.3c02396       



BRD-SF2:  This unoptimized BRD degrader was recently disclosed by scientists at GSK and the Molecular Sciences Research Hub at Imperial College to highlight their VHL-covalent PROTAC technology. The advantages of an E3 covalent PROTAC are obvious, binary vs ternary complex formation while maintaining the potential for catalytic degradation (dependant on coopted E3 ligase protein turnover). While a handful of cysteine-targeting covalent PROTACS have been reported previously, this technology targets Ser110 in the HIFα  binding site of VHL. The challenge, balancing the reactivity profile of the warhead (WH) to modify serine while resisting hydrolysis under physiological conditions. Using a structure guided design approach, the team was able to pick out a viable WH attachment point that maintained critical non-covalent interactions between VH032 (VHL ligand) and its target. Sulfonyl fluoride was proposed as the best WH for modifying Ser110, however, incorporation was met with some difficulty. Specifically, preliminary conditions to generate the sulfonyl fluoride led to epimerization of the proline substituent of the VHL ligand. Fortunately, milder conditions using Selectfluor were developed to mitigate the observed racemization. With the WH in place, further optimization of the ligand, culminating in the introduction of the isoxazole, enhanced target engagement to a point where activity could be assessed. PROTACs targeting BRD4 and androgen receptor (AR) were prepared. For the sake of brevity, results for the BRD4 PROTAC (BRD-SF2) are discussed in detail. For BRD-SF2, dependence on the ubiquitin-proteosome system (UPS) was confirmed with inhibitors of proteosome activity (epoxomicin) and NEDDylation (MLN4924). A head-to-head comparison with MZ-1 (a non-covalent BRD4 PROTAC) revealed inferior degradation efficiency (compared to MZ-1). However, in wash-out experiments, the relative reduction in degradation was less for BRD-SF2 (27%) compared to MZ-1 (48%), indicating the persistence of a covalently modified degradation complex. This result highlights the therapeutic advantage of covalent E3 ligase recruiters. Taken together, initial results from these unoptimized covalent PROTACs look promising. Further optimization of the covalent VHL recruiting ligand will undoubtably furnish a useful tool for targeted protein degradation research.

Reference: https://doi.org/10.1021/acs.jmedchem.3c02123



BIO-7488: Interleukin receptor-associated kinase 4 (IRAK4) plays a key role in the regulation of proinflammatory mediators in response to tissue injury. While numerous peripherally restricted inhibitors have been developed for arthritis indications, CNS penetrant drugs targeting IRAK4 have not received a lot of attention. Researchers at Biogen recognized the link between IRAK4 signalling and the progression of inflammation-mediated neurodegeneration post acute ischemic stroke (AIS). As such, they embarked to develop a brain-penetrant small molecule for the treatment of inflammation post stroke. Their medicinal chemistry campaign produced a molecule with interesting structural features. For instance, the terminal bridged-cyclic ether is a substituent that is rarely seen. It was incorporated to engage in solvent-facing interactions and shown to be less susceptible to oxidative metabolism compared to the other groups considered. Placement of the amide was crucial as its oxygen made a key H-bonding interaction with the hinge Met265. The isopropoxy substituent helped with initial amide hydrolysis issues and contributed, in part, to IRAK4 inhibition. The right-hand aromatic group was optimized to confer greater activity and target specificity. This was attributed to interactions between the pyrazolopyrimidine nitrogen and Val263 (water-bridged interaction), as well as  π-stacking interactions with gatekeeper residue Tyr262. In biochemical assays, BIO-7488 inhibited IRAK4 function at sub-nanomolar concentrations (IC50 = 0.5 nM). Exquisite selectivity was demonstrated in a Kinomescan Assay (Eurofins) where MEK5 was the only other protein identified as a significant binder (>80% at 1 μM). Pharmacokinetic characterization revealed great oral bioavailability across species (F(%) = 91/98/95/96 in rat/mouse/monkey/dog). Follow-up safety studies did not identify any concerns related to genotoxicity (negative Ames and micronucleus tests) and cardiac safety ( hERG IC50 > 30 μM, Cav1.2/Nav1.5 IC50 > 10 μM). Pharmacodynamic efficacy was assessed in a mouse LPS challenge model. In the model, dose-dependent suppression of inflammatory cytokines IL-1β, TNFα, and IL-6 was observed with plasma cytokine concentration being reduced to levels comparable to control groups at the lowest dose tested (10 mg/kg, i.p.).    Given its clean safety profile and favourable PD, it’s likely that BIO-7488 will undergo further preclinical evaluation to enable Phase I trials.              

Reference: https://doi.org/10.1021/acs.jmedchem.3c02226

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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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