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

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

CMX990
CMX990

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

BAY-9835
BAY-9835

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

ACT-1016-0707
ACT-1016-0707

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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Alessandro Monge, PhD

Strategic Business Development Advisor

Dr. Alessandro Monge is a business strategist with over 20 years of experience at the intersection of computational science, artificial intelligence, and drug discovery. He serves as Strategic Business Development Advisor to Dalriada Drug Discovery, where he contributes to the company’s growth by supporting strategic partnerships, refining market positioning, and aligning platform innovation with emerging trends in therapeutics. In parallel, he is Managing Partner at Blue Dolphin, a consultancy focused on corporate and business development in AI-driven drug discovery, where he advises leadership teams on strategic execution, fundraising, and commercial expansion.

 

With a foundation in quantum mechanics, statistical mechanics, molecular dynamics, and protein modeling, Alessandro brings scientific depth to business leadership. In addition to Dalriada, he serves as Strategic Business Advisor to innovative companies including Pharmacelera and Nanome. He previously held senior management positions at Schrodinger, Iktos and TandemAI.

 

Alessandro earned his PhD in theoretical physics from The Rockefeller University and conducted postdoctoral research at Columbia University, where he developed algorithms for protein structure prediction. A trusted advisor and thought partner in the biotech and AI-driven discovery space, Alessandro is committed to advancing transformative science through impactful business execution.

Kanchan Devkota, PhD

Associate Director, Biochem, Biophysics & MS

Kanchan Devkota is a versatile biochemist and biophysicist with over 10 years of experience in protein sciences, assay development, and small molecule drug discovery. As Associate Director of Biochemistry, Biophysics & Protein Mass Spectrometry at Dalriada Drug Discovery, he leads integrated teams driving biochemical and biophysical assay development, hit validation, and mass spectrometry-based analytics to support a wide range of therapeutic programs.

Dr. Devkota’s core expertise includes high-throughput screening, enzymology, and quantitative biophysics—spanning technologies such as SPR, ITC, DSF, DSLS, MST and intact mass spectrometry. A certified Radiation Safety Officer at Dalriada, he also brings specialized capabilities in radioligand binding and functional assays. His work has accelerated programs targeting epigenetic modulators, oxidoreductases, and protein-protein interactions across oncology, infectious diseases, and beyond.

He earned his PhD in Biomedicine from the University of Copenhagen (Novo Nordisk Foundation Center for Protein Research), where he focused on protein structure and function. He subsequently held postdoctoral fellowships at the University of Copenhagen and the Structural Genomics Consortium (University of Toronto), contributing to probe discovery for SARS-CoV-2 and cancer targets in collaboration with global pharmaceutical companies including Pfizer, Takeda, BI and Merck.

Since joining Dalriada, Dr. Devkota has played an instrumental role in shaping the company’s scientific direction and partner-driven innovation. His leadership spans not only scientific execution but also business development, client engagement, and project strategy.

An advocate for translational science and collaborative research, Dr. Devkota has published > 10 publications in high-impact journals and remains actively involved in the scientific community through presentations and cross-functional partnerships. His multidisciplinary background and solution-oriented mindset continue to help advance drug discovery initiatives from concept to hit candidates.

Kashif Aziz Khan, PhD

Associate Director, Cell Biology

Kashif Aziz Khan is a seasoned cell and molecular biologist with over 20 years of experience in research and drug discovery. As Associate Director of Cell Biology at Dalriada Drug Discovery, he leads a dynamic, high-performing team at the forefront of developing innovative cell-based assays and advancing small molecule therapeutics targeting oncology, inflammation, GPCRs, and more.

Dr. Khan’s expertise lies in designing, optimizing, and validating high-throughput and mechanistically relevant assays to accelerate lead identification, target engagement, and protein degradation workflows. His strategic leadership and scientific rigor have significantly contributed to the progress of preclinical drug discovery pipelines.

He earned his PhD in Cell and Molecular Biology from the University of Franche-Comté, France, followed by a postdoctoral fellowship at the University of Montreal, where he investigated antiviral innate immune responses and contributed high-throughput screening technologies for novel therapeutic targets.

Prior to joining Dalriada, Dr. Khan led a graduate research lab at York University, managing interdisciplinary projects, securing competitive research funding, and mentoring emerging scientists. His academic and industry experience spans key areas including cell signaling, gene regulation in cancer, epigenetics, and innate immunity.

A prolific contributor to the scientific community, Dr. Khan has authored over 25 peer-reviewed publications and presented at numerous international conferences. Fluent in English and French, he is deeply committed to mentorship, scientific collaboration, and fostering innovation across the biomedical research landscape.

Peter J. Brown, PhD

Scientific Partnerships Lead

Peter Brown is a seasoned medicinal chemist and drug discovery leader with over 30 years of experience spanning large pharma, academic-industry collaborations, and global research consortia. He brings deep scientific expertise and a strong biopharma network to help advance Dalriada’s mission and extend the reach of its innovative platforms in North America. 

At Dalriada, Peter focuses on forging strategic partnerships, identifying collaborative opportunities, and supporting the scientific positioning of key platform technologies, including iCLASS.  

Prior to joining Dalriada, Peter held senior scientific roles at the Structural Genomics Consortium (SGC), where he helped establish the organization as a global leader in epigenetic chemical probe discovery. He played a central role in managing complex, multi-partner projects between academia and industry, and most recently organized antiviral probe discovery efforts at the SGC site at the University of North Carolina at Chapel Hill, contributing to the NIH’s AViDDprogram. 

Earlier in his career, Peter spent 19 years at GlaxoSmithKline, where he held various leadership positions in medicinal chemistry, including Section Head. His work focused on early-stage drug discovery and tool compound development, particularly within the Nuclear Receptor family. 

Peter earned his Ph.D. in Organic Chemistry from the University of Sheffield and completed postdoctoral research at Indiana University under Professor Philip Magnus, where he completed the total synthesis of (-)-Pleiomutine. He is a co-author of over 140 peer-reviewed publications, holds 9 patents, and has delivered more than 25 invited presentations at international scientific meetings. 

His areas of expertise include high-throughput screening, target-focused compound libraries, DNA-encoded libraries, and fragment-based drug discovery. 

Taleb Sedighi, PhD

Director, Proteomics

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.

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.

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Mohammad Eram, PhD

Senior Director, Discovery R&D

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, 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, 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, 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.

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, 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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