UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): November 30, 2020
COGENT BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-38443 | 46-5308248 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) | ||
| 200 Cambridge Park Drive, Suite 2500 Cambridge, Massachusetts |
02140 | |||
| (Address of principal executive offices) | (Zip Code) | |||
Registrant’s telephone number, including area code (617) 945-5576
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
| Common stock, $0.001 Par Value | COGT | The Nasdaq Global Select Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
Item 8.01 Other Events.
On November 30, 2020, Cogent Biosciences, Inc. (the “Company”) made available on its website at https://www.cogentbio.com in the investor relations section an updated corporate presentation, a copy of which is filed as Exhibit 99.1 hereto and is incorporated by reference herein.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Cogent Biosciences, Inc. Corporate Presentation. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: November 30, 2020 | COGENT BIOSCIENCES, INC. | |||||
| By: | /s/ John Green | |||||
| John Green | ||||||
| Chief Financial Officer | ||||||
Exhibit 99.1 Developing Precision therapies for genetically defined diseases Corporate Presentation Q4 2020Exhibit 99.1 Developing Precision therapies for genetically defined diseases Corporate Presentation Q4 2020
Forward‐Looking Statements and Risk Factors This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, any statements of the plans, strategies, and objectives of management for future operations, including our clinical development and commercialization plans; any projections of financial information; any statement about historical results that may suggest trends for our business; any statement of expectation or belief regarding future events; potential markets or market size, technology developments, our clinical product pipeline, clinical data or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; any statements regarding the anticipated benefits of our collaborations or other strategic transactions; and any statements of assumptions underlying any of the items mentioned. These statements are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited to, risks associated with: the potential impacts of raising additional capital, including dilution to our existing stockholders, restrictions our operations or requirements that we relinquish rights to our technologies or product candidates; business interruptions resulting from the coronavirus disease outbreak or similar public health crises, which could cause a disruption of the development of our product candidates and adversely impact our business; the success, cost, and timing of our product development activities and clinical trials; the timing of our planned regulatory submissions to the FDA for our product candidate PLX9486 and feedback from the FDA as to our plans; our ability to obtain and maintain regulatory approval for our PLX9486 product candidate and any other product candidates we may develop, and any related restrictions, limitations, and/or warnings in the label of an approved product candidate; the potential for our identified research priorities to advance our PLX9486 product candidate; the ability to license additional intellectual property relating to our product candidates from third-parties and to comply with our existing license agreements and collaboration agreements; the ability and willingness of our third-party research institution collaborators to continue research and development activities relating to our product candidates; our ability to commercialize our products in light of the intellectual property rights of others; our ability to obtain funding for our operations, including funding necessary to complete further development and commercialization of our product candidates; the scalability and commercial viability of our manufacturing methods and processes; the commercialization of our product candidates, if approved;our plans to research, develop, and commercialize our product candidates; our ability to attract collaborators with development, regulatory, and commercialization expertise; our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates; among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our periodic filings filed from time to time with the Securities and Exchange Commission. Unless as required by law, we assume no obligation and do not intend to update these forward-looking statements or to conform these statements to actual results or to changes in our expectations. All of Cogent Biosciences (“Cogent”) product candidates are investigational product candidates and their safety and efficacy have not yet been established. Cogent has not obtained marketing approval for any product, and there is no certainty that any marketing approvals will be obtained or as to the timelines on which they will be obtained. Any data pertaining to Cogent product candidates is interim data and may include investigator-reported interim data for which Cogent has not yet independently reviewed the source data. The interim data may not be representative of the final results that may be obtained in the corresponding trials and results from earlier trials may not be representative of results obtained in later trial or pivotal trials. 2Forward‐Looking Statements and Risk Factors This presentation and the accompanying oral commentary contain forward-looking statements that involve risks, uncertainties and assumptions. If the risks or uncertainties ever materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward looking statements. All statements other than statements of historical fact could be deemed forward-looking, including, but not limited to, any statements of the plans, strategies, and objectives of management for future operations, including our clinical development and commercialization plans; any projections of financial information; any statement about historical results that may suggest trends for our business; any statement of expectation or belief regarding future events; potential markets or market size, technology developments, our clinical product pipeline, clinical data or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; any statements regarding the anticipated benefits of our collaborations or other strategic transactions; and any statements of assumptions underlying any of the items mentioned. These statements are based on estimates and information available to us at the time of this presentation and are not guarantees of future performance. Actual results could differ materially from our current expectations as a result of many risks and uncertainties, including but not limited to, risks associated with: the potential impacts of raising additional capital, including dilution to our existing stockholders, restrictions our operations or requirements that we relinquish rights to our technologies or product candidates; business interruptions resulting from the coronavirus disease outbreak or similar public health crises, which could cause a disruption of the development of our product candidates and adversely impact our business; the success, cost, and timing of our product development activities and clinical trials; the timing of our planned regulatory submissions to the FDA for our product candidate PLX9486 and feedback from the FDA as to our plans; our ability to obtain and maintain regulatory approval for our PLX9486 product candidate and any other product candidates we may develop, and any related restrictions, limitations, and/or warnings in the label of an approved product candidate; the potential for our identified research priorities to advance our PLX9486 product candidate; the ability to license additional intellectual property relating to our product candidates from third-parties and to comply with our existing license agreements and collaboration agreements; the ability and willingness of our third-party research institution collaborators to continue research and development activities relating to our product candidates; our ability to commercialize our products in light of the intellectual property rights of others; our ability to obtain funding for our operations, including funding necessary to complete further development and commercialization of our product candidates; the scalability and commercial viability of our manufacturing methods and processes; the commercialization of our product candidates, if approved;our plans to research, develop, and commercialize our product candidates; our ability to attract collaborators with development, regulatory, and commercialization expertise; our expectations regarding our ability to obtain and maintain intellectual property protection for our product candidates; among others. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our periodic filings filed from time to time with the Securities and Exchange Commission. Unless as required by law, we assume no obligation and do not intend to update these forward-looking statements or to conform these statements to actual results or to changes in our expectations. All of Cogent Biosciences (“Cogent”) product candidates are investigational product candidates and their safety and efficacy have not yet been established. Cogent has not obtained marketing approval for any product, and there is no certainty that any marketing approvals will be obtained or as to the timelines on which they will be obtained. Any data pertaining to Cogent product candidates is interim data and may include investigator-reported interim data for which Cogent has not yet independently reviewed the source data. The interim data may not be representative of the final results that may be obtained in the corresponding trials and results from earlier trials may not be representative of results obtained in later trial or pivotal trials. 2
Cogent Biosciences: Emerging Leader in Precision Medicines for Genetically Defined Diseases PLX9486, a potential best-in-class KIT exon 17 inhibitor, has demonstrated promising clinical efficacy and safety results in a Phase 1/2 clinical trial in patients with gastrointestinal stromal tumors (GIST), along with accelerated timelines to proof-of-concept in systemic mastocytosis 1H 2021 2H 2021 Broad clinical development plan Initiate ASM clinical trial designed to move PLX9486 rapidly Initiate randomized GIST clinical trial to high unmet need patient populations Initiate ISM clinical trial 2021+ Strategy Create pipeline of additional highly selective, potent compounds Cogent is well capitalized with $129.4 million as of September 30, 2020 3Cogent Biosciences: Emerging Leader in Precision Medicines for Genetically Defined Diseases PLX9486, a potential best-in-class KIT exon 17 inhibitor, has demonstrated promising clinical efficacy and safety results in a Phase 1/2 clinical trial in patients with gastrointestinal stromal tumors (GIST), along with accelerated timelines to proof-of-concept in systemic mastocytosis 1H 2021 2H 2021 Broad clinical development plan Initiate ASM clinical trial designed to move PLX9486 rapidly Initiate randomized GIST clinical trial to high unmet need patient populations Initiate ISM clinical trial 2021+ Strategy Create pipeline of additional highly selective, potent compounds Cogent is well capitalized with $129.4 million as of September 30, 2020 3
PLX9486: Next‐Generation KIT exon 17 InhibitorPLX9486: Next‐Generation KIT exon 17 Inhibitor
PLX9486 is a Highly Selective and Potent KIT Mutant Inhibitor with Potential to Demonstrate Best-in-Class Clinical Profile PLX9486 Encouraging Clinical Activity 12 months mPFS demonstrated with combination of • Specifically targets KIT exon 17 D816V PLX9486 + sunitinib in heavily pre-treated GIST patients mutations • Selective versus other targets including wild-type KIT, PDGFRα, VEGFR2, FLT3 Attractive Emerging Safety Profile and FMS Well tolerated with no significant safety signals across 50+ patients in single agent & combination dosing • Worldwide rights to compound exclusively 1 licensed from Plexxikon Potential Best-in-Class KIT exon 17 inhibitor 2 • Patent protection through at least 2033 KIT D816V inhibition supports future studies in systemic mastocytosis and GIST; safety results support potential for broad use 1 Plexxikon is eligible for mid- to high- single-digit royalties and additional development milestones. License includes rights to PLX0206, an additional selective KIT inhibitor in preclinical development 5 2 Does not include available patent term extensionPLX9486 is a Highly Selective and Potent KIT Mutant Inhibitor with Potential to Demonstrate Best-in-Class Clinical Profile PLX9486 Encouraging Clinical Activity 12 months mPFS demonstrated with combination of • Specifically targets KIT exon 17 D816V PLX9486 + sunitinib in heavily pre-treated GIST patients mutations • Selective versus other targets including wild-type KIT, PDGFRα, VEGFR2, FLT3 Attractive Emerging Safety Profile and FMS Well tolerated with no significant safety signals across 50+ patients in single agent & combination dosing • Worldwide rights to compound exclusively 1 licensed from Plexxikon Potential Best-in-Class KIT exon 17 inhibitor 2 • Patent protection through at least 2033 KIT D816V inhibition supports future studies in systemic mastocytosis and GIST; safety results support potential for broad use 1 Plexxikon is eligible for mid- to high- single-digit royalties and additional development milestones. License includes rights to PLX0206, an additional selective KIT inhibitor in preclinical development 5 2 Does not include available patent term extension
PLX9486 Designed as Potent and Selective KIT exon 17 D816V Inhibitor PLX9486 is a Type I Inhibitor designed to selectively bind the active conformation of mutant KIT • Comparable potency observed relative to avapritinib with potential selectivity advantages • Limited blood-brain-barrier penetration and no CNS toxicities identified in preclinical studies Potency Selectivity IC50 (nM) IC50 (nM) Enzyme Assay PLX9486 PLX9486 Avapritinib >5000* c-Kit (wt) KIT D814Y autophosphorylation 12 22 c-Kit (D816V) 1.125 a (murine P815 cells) FMS 602.4 b BA/F3 KIT D816V growth 12 13.5 KDR/VEGFR2 >5000* b KIT D816V kinase activity (Reaction Bio) 1.125 0.4143 PDGFRα >5000* a Comparison of PLX9486 data with previously published avapritinib data PDGFRα (D842V) 104.3 b Direct comparison within experiments using non‐GMP syntheses Note: No head‐to‐head clinical trials have been conducted between PLX9486 and avapritinib. *Highest concentration tested in biochemical assay 6PLX9486 Designed as Potent and Selective KIT exon 17 D816V Inhibitor PLX9486 is a Type I Inhibitor designed to selectively bind the active conformation of mutant KIT • Comparable potency observed relative to avapritinib with potential selectivity advantages • Limited blood-brain-barrier penetration and no CNS toxicities identified in preclinical studies Potency Selectivity IC50 (nM) IC50 (nM) Enzyme Assay PLX9486 PLX9486 Avapritinib >5000* c-Kit (wt) KIT D814Y autophosphorylation 12 22 c-Kit (D816V) 1.125 a (murine P815 cells) FMS 602.4 b BA/F3 KIT D816V growth 12 13.5 KDR/VEGFR2 >5000* b KIT D816V kinase activity (Reaction Bio) 1.125 0.4143 PDGFRα >5000* a Comparison of PLX9486 data with previously published avapritinib data PDGFRα (D842V) 104.3 b Direct comparison within experiments using non‐GMP syntheses Note: No head‐to‐head clinical trials have been conducted between PLX9486 and avapritinib. *Highest concentration tested in biochemical assay 6
Dual-conformation KIT Inhibition Drives Tumor Regression in Heterogeneous GIST mouse models Ex11 (W557_K558del), Ex17 (N822K) Ex13 (K642E), Ex17 (D823Y) 7Dual-conformation KIT Inhibition Drives Tumor Regression in Heterogeneous GIST mouse models Ex11 (W557_K558del), Ex17 (N822K) Ex13 (K642E), Ex17 (D823Y) 7
Systemic Mastocytosis& KIT exon 17 D816V mutationsSystemic Mastocytosis& KIT exon 17 D816V mutations
Significant Unmet Need Remains for Neurological Headache, brain fog, Systemic Mastocytosis Patients cognitive dysfunction, anxiety, depression Systemic Mastocytosis Systemic • Disease driven by over-accumulation of mast Anaphylaxis cells across various internal organs in the body Cutaneous (skin) Advanced Systemic Mastocytosis (ASM) Flushing of the face/neck/chest, hives, skin rashes, itching with or without rash • Median survival of approximately ≤ 3.5 years • FDA approved drug, Rydapt (Midostaurin), Gastrointestinal broad spectrum TKI, challenging tolerability Diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD) Indolent and Smoldering Mastocytosis (ISM) • Significantly impacts quality of life • No approved therapies: current treatments Other include H1 and H2 anti-histamines, mast cell Cardiovascular Skeletal Light-headedness, syncope (fainting), stabilizers, leukotriene inhibitors Bone/muscle pain, rapid heart rate, chest pain, low blood osteopenia, osteoporosis pressure, high blood pressure at Gynecological reaction start, blood pressure instability Uterine cramps, bleeding Ear/Nose/Throat/Respiratory Urinary Nasal itching and congestion, throat Bladder irritability, frequent itching and swelling, wheezing, voiding shortness of breathSignificant Unmet Need Remains for Neurological Headache, brain fog, Systemic Mastocytosis Patients cognitive dysfunction, anxiety, depression Systemic Mastocytosis Systemic • Disease driven by over-accumulation of mast Anaphylaxis cells across various internal organs in the body Cutaneous (skin) Advanced Systemic Mastocytosis (ASM) Flushing of the face/neck/chest, hives, skin rashes, itching with or without rash • Median survival of approximately ≤ 3.5 years • FDA approved drug, Rydapt (Midostaurin), Gastrointestinal broad spectrum TKI, challenging tolerability Diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD) Indolent and Smoldering Mastocytosis (ISM) • Significantly impacts quality of life • No approved therapies: current treatments Other include H1 and H2 anti-histamines, mast cell Cardiovascular Skeletal Light-headedness, syncope (fainting), stabilizers, leukotriene inhibitors Bone/muscle pain, rapid heart rate, chest pain, low blood osteopenia, osteoporosis pressure, high blood pressure at Gynecological reaction start, blood pressure instability Uterine cramps, bleeding Ear/Nose/Throat/Respiratory Urinary Nasal itching and congestion, throat Bladder irritability, frequent itching and swelling, wheezing, voiding shortness of breath
Systemic Mastocytosis (SM): Primarily Driven by KIT exon 17 D816V Mutations KIT exon 17 D816V mutation is 1 detected in >90% of SM patients o Occurs within the activation loop domain and causes a conformational change in the enzymatic pocket of the receptor o This conformational change results in ligand independent constitutive activation of KIT and leads to increased proliferation Inhibition of KIT exon 17 mutations has shown clinical activity in both ASM and ISM 1 10 https://www.nejm.org/doi/full/10.1056/NEJMoa1513098Systemic Mastocytosis (SM): Primarily Driven by KIT exon 17 D816V Mutations KIT exon 17 D816V mutation is 1 detected in >90% of SM patients o Occurs within the activation loop domain and causes a conformational change in the enzymatic pocket of the receptor o This conformational change results in ligand independent constitutive activation of KIT and leads to increased proliferation Inhibition of KIT exon 17 mutations has shown clinical activity in both ASM and ISM 1 10 https://www.nejm.org/doi/full/10.1056/NEJMoa1513098
Large, Yet Not Well Understood Population of SM Patients Systemic Mastocytosis: Estimated prevalence in the U.S. is 20,000–30,000 patients ISM Significant unmet medical need Comprises upwards of for clinically active, well tolerated 1 90% of all cases of SM treatment options for this patient population ASM 1 11 https://www.sciencedirect.com/science/article/abs/pii/S0145212619300566Large, Yet Not Well Understood Population of SM Patients Systemic Mastocytosis: Estimated prevalence in the U.S. is 20,000–30,000 patients ISM Significant unmet medical need Comprises upwards of for clinically active, well tolerated 1 90% of all cases of SM treatment options for this patient population ASM 1 11 https://www.sciencedirect.com/science/article/abs/pii/S0145212619300566
PLX9486 Positioned to Move Rapidly Into ASM and ISM Clinical Studies Pre-clinical KIT selectivity and potency along with clinical experience – safety + target engagement Phase 2 start as single agent in Phase 2 start as single agent in Advanced Indolent Systemic Mastocytosis (ASM) Systemic Mastocytosis (ISM) (1H’2021) (2H’2021) Serum tryptase level is used as diagnostic marker for SM patients and considered to reflect the burden of mast cells… …will provide a well understood and accepted marker for assessing clinical proof of concept based on planned ASM & ISM clinical trials 12PLX9486 Positioned to Move Rapidly Into ASM and ISM Clinical Studies Pre-clinical KIT selectivity and potency along with clinical experience – safety + target engagement Phase 2 start as single agent in Phase 2 start as single agent in Advanced Indolent Systemic Mastocytosis (ASM) Systemic Mastocytosis (ISM) (1H’2021) (2H’2021) Serum tryptase level is used as diagnostic marker for SM patients and considered to reflect the burden of mast cells… …will provide a well understood and accepted marker for assessing clinical proof of concept based on planned ASM & ISM clinical trials 12
GIST & KIT exon 13/17 mutationsGIST & KIT exon 13/17 mutations
Significant Unmet Need Remains for GIST Patients Gastrointestinal Stromal Tumor (GIST) • Between 4,000 to 6,000 GIST cases diagnosed each year 1 in the United States • Tumors can start anywhere in the GI tract, but they occur most often in the stomach (about 60%) or the small 4 Symptoms 2 intestine (about 35%) Diarrhea, Nausea, 3 Vomiting, Abdominal • 83% 5-year survival rate Pain, Bloating, • Current FDA approved therapies include Imatinib, Sunitinib, Gastroesophageal reflux disease GERD, Regorafenib, and Ripretinib GI bleeding, Loss of • 60% of GIST patients develop resistance to imatinib appetite, Weight loss 1 (10% primary, 50% secondary resistance) 1 https://clincancerres.aacrjournals.org/content/15/24/7510 2 https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/about/key-statistics.html 3 https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/detection-diagnosis-staging/survival-rates.html 4 https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/detection-diagnosis-staging/signs-symptoms.html Significant Unmet Need Remains for GIST Patients Gastrointestinal Stromal Tumor (GIST) • Between 4,000 to 6,000 GIST cases diagnosed each year 1 in the United States • Tumors can start anywhere in the GI tract, but they occur most often in the stomach (about 60%) or the small 4 Symptoms 2 intestine (about 35%) Diarrhea, Nausea, 3 Vomiting, Abdominal • 83% 5-year survival rate Pain, Bloating, • Current FDA approved therapies include Imatinib, Sunitinib, Gastroesophageal reflux disease GERD, Regorafenib, and Ripretinib GI bleeding, Loss of • 60% of GIST patients develop resistance to imatinib appetite, Weight loss 1 (10% primary, 50% secondary resistance) 1 https://clincancerres.aacrjournals.org/content/15/24/7510 2 https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/about/key-statistics.html 3 https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/detection-diagnosis-staging/survival-rates.html 4 https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/detection-diagnosis-staging/signs-symptoms.html
Mutations in KIT exon 13 and KIT exon 17 are Key Drivers of Resistance ORR ORR ORR ORR ~60% ~7% PFS ~5% PFS ~9% 1L 2L 3L 4L PFS ~19 ~6 ~4.8 PFS ~6.3 months months months months Imatinib Sunitinib Regorafenib Ripretinib 60% of GIST patients Resistance mutations 2,000-3,500 imatinib- develop resistance to driven by KIT exon 13 resistant, annual treatable 1 1 Imatinib. and KIT exon 17 GIST patients. 1 https://clincancerres.aacrjournals.org/content/15/24/7510 15Mutations in KIT exon 13 and KIT exon 17 are Key Drivers of Resistance ORR ORR ORR ORR ~60% ~7% PFS ~5% PFS ~9% 1L 2L 3L 4L PFS ~19 ~6 ~4.8 PFS ~6.3 months months months months Imatinib Sunitinib Regorafenib Ripretinib 60% of GIST patients Resistance mutations 2,000-3,500 imatinib- develop resistance to driven by KIT exon 13 resistant, annual treatable 1 1 Imatinib. and KIT exon 17 GIST patients. 1 https://clincancerres.aacrjournals.org/content/15/24/7510 15
Gastrointestinal Stromal Tumor (GIST): Imatinib-resistance linked to KIT exon 13 and KIT exon 17 mutations Imatinib-resistant patients most commonly exhibited secondary KIT 1 exon 13 and/or KIT exon 17 mutations • 15-26 different mutations were found in KIT exons 17/18 in both tumor and liquid biopsies • 5-12 different mutations were found in KIT exons 13/14 in both tumor and liquid biopsies These study results support that there is a strong biologic rationale to treat imatinib- resistant GIST patients with combination of PLX9486 (KIT exon 17 inhibitor) + sunitinib (KIT exon 13 inhibitor) 1 16 Deciphera CTOS Annual Meeting 2020, November 17, 2020Gastrointestinal Stromal Tumor (GIST): Imatinib-resistance linked to KIT exon 13 and KIT exon 17 mutations Imatinib-resistant patients most commonly exhibited secondary KIT 1 exon 13 and/or KIT exon 17 mutations • 15-26 different mutations were found in KIT exons 17/18 in both tumor and liquid biopsies • 5-12 different mutations were found in KIT exons 13/14 in both tumor and liquid biopsies These study results support that there is a strong biologic rationale to treat imatinib- resistant GIST patients with combination of PLX9486 (KIT exon 17 inhibitor) + sunitinib (KIT exon 13 inhibitor) 1 16 Deciphera CTOS Annual Meeting 2020, November 17, 2020
Phase 1/2 Study of PLX9486 + sunitinib in Heavily Pre‐Treated GIST PatientsPhase 1/2 Study of PLX9486 + sunitinib in Heavily Pre‐Treated GIST Patients
Study PLX121-01: Phase 1/2 Study of PLX9486 + Sunitinib Part 2e: PLX9486 + Sunitinib Eligibility Dose Level 3 • Relapsed/Refractory GIST Dose Level 1 (N=3) Dose Level 2 (N=5) (N=10) • Previous imatinib treatment PLX9486: 500mg PLX9486: 1000mg PLX9486: 1000mg Sunitinib: 25 mg Sunitinib: 25 mg Sunitinib: 37.5 mg Design for Part 2e • 3+3 dose escalation All doses PO once daily • 3 combination dose levels based on PLX9486 single agent experience Criteria for Dose Limiting Toxicities Assessed during Cycle 1 (28 days) NCT#02401815 Nonhematologic Primary Objective • Gr ≥ 3 AE of laboratory toxicity despite adequate supportive care Characterize the safety and tolerability of combination in patients with GIST Secondary Objectives Overall response rate per RECIST v1.1 Hematologic Clinical benefit rate (CBR): CR + PR + SD ≥ 16 weeks • Gr 4 anemia, neutropenia, or Exploratory Objective thrombocytopenia Changes in circulating tumor DNA (ctDNA) and correlation with response and survival • Gr 3 neutropenia/thrombocytopenia lasting > 7 days 18Study PLX121-01: Phase 1/2 Study of PLX9486 + Sunitinib Part 2e: PLX9486 + Sunitinib Eligibility Dose Level 3 • Relapsed/Refractory GIST Dose Level 1 (N=3) Dose Level 2 (N=5) (N=10) • Previous imatinib treatment PLX9486: 500mg PLX9486: 1000mg PLX9486: 1000mg Sunitinib: 25 mg Sunitinib: 25 mg Sunitinib: 37.5 mg Design for Part 2e • 3+3 dose escalation All doses PO once daily • 3 combination dose levels based on PLX9486 single agent experience Criteria for Dose Limiting Toxicities Assessed during Cycle 1 (28 days) NCT#02401815 Nonhematologic Primary Objective • Gr ≥ 3 AE of laboratory toxicity despite adequate supportive care Characterize the safety and tolerability of combination in patients with GIST Secondary Objectives Overall response rate per RECIST v1.1 Hematologic Clinical benefit rate (CBR): CR + PR + SD ≥ 16 weeks • Gr 4 anemia, neutropenia, or Exploratory Objective thrombocytopenia Changes in circulating tumor DNA (ctDNA) and correlation with response and survival • Gr 3 neutropenia/thrombocytopenia lasting > 7 days 18
Demographics and Prior Therapy: Heavily Pretreated GIST Patients Total Dose Level 1 Dose Level 2 Dose Level 3 (N=18) (n=3) (n=5) (n=10) Age, Median (range) 62 (44 – 78) 57 (46 – 68) 55 (44 – 78) 62 (53 – 65) Sex, male, n (%) 9 (50) 0 3 (60) 6 (60) Prior Regimens, Median (range) 3 (1 – 6) 2 (1 – 2) 3 (1 – 6) 4 (1 – 5) Imatinib, n (%) 18 (100) 3 (100) 5 (100) 10 (100) Sunitinib, n (%) 13 (72) 1 (33) 4 (80) 8 (80) Regorafenib, n (%) 12 (67) 0 4 (80) 8 (80) Ripretinib, n (%) 5 (28) 1 (33) 1 (20) 3 (30) ≥ 3 prior lines, n (%) 12 (67) 0 4 (80) 8 (80) Prior treatment with PLX9486 3 (17) 00 3 (30) (previously enrolled on another arm) DL 1 = PLX9486 500 mg + Sunitinib 25 mg; DL 2 = PLX9486 1000 mg + Sunitinib 25 mg; DL3 = PLX9486 1000 mg + Sunitinib 37.5 mg All doses PO once daily db snapshot: 10July2020 19Demographics and Prior Therapy: Heavily Pretreated GIST Patients Total Dose Level 1 Dose Level 2 Dose Level 3 (N=18) (n=3) (n=5) (n=10) Age, Median (range) 62 (44 – 78) 57 (46 – 68) 55 (44 – 78) 62 (53 – 65) Sex, male, n (%) 9 (50) 0 3 (60) 6 (60) Prior Regimens, Median (range) 3 (1 – 6) 2 (1 – 2) 3 (1 – 6) 4 (1 – 5) Imatinib, n (%) 18 (100) 3 (100) 5 (100) 10 (100) Sunitinib, n (%) 13 (72) 1 (33) 4 (80) 8 (80) Regorafenib, n (%) 12 (67) 0 4 (80) 8 (80) Ripretinib, n (%) 5 (28) 1 (33) 1 (20) 3 (30) ≥ 3 prior lines, n (%) 12 (67) 0 4 (80) 8 (80) Prior treatment with PLX9486 3 (17) 00 3 (30) (previously enrolled on another arm) DL 1 = PLX9486 500 mg + Sunitinib 25 mg; DL 2 = PLX9486 1000 mg + Sunitinib 25 mg; DL3 = PLX9486 1000 mg + Sunitinib 37.5 mg All doses PO once daily db snapshot: 10July2020 19
Combination Safety Results Generally Similar to Single-Agent sunitinib observed in a separate, third-party clinical study Total Dose Level 1 Dose Level 2 Dose Level 3 (n=18) (n=3) (n=5) (n=10) Preferred term, n Any Gr Gr ≥ 3 Any Gr Gr ≥ 3Any Gr Gr ≥ 3 Any Gr Gr ≥ 3 Any AE 18 16 3 2 5 5 10 9 Diarrhea 13 2 3 0 2 1 8 1 Anemia 9 5 3 1 2 1 4 3 Hypophosphatemia 7 3 1 1 3 1 3 1 Fatigue 7 2 1 0 2 0 4 2 Hypertension 7 2 0 0 3 2 4 0 Lymphopenia 3 2 1 0 0 0 2 2 DL 1 = PLX9486 500 mg + Sunitinib 25 mg; DL 2 = PLX9486 1000 mg + Sunitinib 25 mg; DL3 = PLX9486 1000 mg + Sunitinib 37.5 mg • Combination safety results generally similar to that of single-agent sunitinib observed in a separate, third-party clinical study (Demetri et al, Lancet 2006) • Results presented from non-head-to-head studies and should be interpreted with caution. • Severe events did not appear to be dose-dependent • Dose modification guidelines for treatment-related AEs allowed majority of patients to remain on treatment – One patient had a treatment-related AE leading to withdrawal of study treatment (gr 3 anemia) – Three patients required dose reduction db snapshot: 10July2020 20 • One AE (sepsis) led to death (not related to study treatment; post-operative complication)Combination Safety Results Generally Similar to Single-Agent sunitinib observed in a separate, third-party clinical study Total Dose Level 1 Dose Level 2 Dose Level 3 (n=18) (n=3) (n=5) (n=10) Preferred term, n Any Gr Gr ≥ 3 Any Gr Gr ≥ 3Any Gr Gr ≥ 3 Any Gr Gr ≥ 3 Any AE 18 16 3 2 5 5 10 9 Diarrhea 13 2 3 0 2 1 8 1 Anemia 9 5 3 1 2 1 4 3 Hypophosphatemia 7 3 1 1 3 1 3 1 Fatigue 7 2 1 0 2 0 4 2 Hypertension 7 2 0 0 3 2 4 0 Lymphopenia 3 2 1 0 0 0 2 2 DL 1 = PLX9486 500 mg + Sunitinib 25 mg; DL 2 = PLX9486 1000 mg + Sunitinib 25 mg; DL3 = PLX9486 1000 mg + Sunitinib 37.5 mg • Combination safety results generally similar to that of single-agent sunitinib observed in a separate, third-party clinical study (Demetri et al, Lancet 2006) • Results presented from non-head-to-head studies and should be interpreted with caution. • Severe events did not appear to be dose-dependent • Dose modification guidelines for treatment-related AEs allowed majority of patients to remain on treatment – One patient had a treatment-related AE leading to withdrawal of study treatment (gr 3 anemia) – Three patients required dose reduction db snapshot: 10July2020 20 • One AE (sepsis) led to death (not related to study treatment; post-operative complication)
PLX9486 + Sunitinib: 12-Month mPFS in Heavily Pretreated GIST Patients • Estimated 12-month mPFS in PLX9486- naïve patients receiving combination • mPFS improvement observed for patients receiving higher dose of single-agent PLX9486 • In subset of patients with ≥ 2 prior therapies (n=11), estimated PFS remains 12 months * 21 * Excludes combination therapy patients who had previously received PLX9486. db snapshot: 10July2020 PLX9486 + Sunitinib: 12-Month mPFS in Heavily Pretreated GIST Patients • Estimated 12-month mPFS in PLX9486- naïve patients receiving combination • mPFS improvement observed for patients receiving higher dose of single-agent PLX9486 • In subset of patients with ≥ 2 prior therapies (n=11), estimated PFS remains 12 months * 21 * Excludes combination therapy patients who had previously received PLX9486. db snapshot: 10July2020
PLX9486 + Sunitinib: Clinical Benefit Observed in Majority of Patients ORR = 20% (1 CR, 2PR) Best Overall Response: CBR = 80% • Excludes combination therapy patients who had previously received PLX9486 ORR: Overall Response Rate (CR+PR) db snapshot: 10July2020 CBR: Clinical benefit rate (CR+PR+SD at 16 weeks)PLX9486 + Sunitinib: Clinical Benefit Observed in Majority of Patients ORR = 20% (1 CR, 2PR) Best Overall Response: CBR = 80% • Excludes combination therapy patients who had previously received PLX9486 ORR: Overall Response Rate (CR+PR) db snapshot: 10July2020 CBR: Clinical benefit rate (CR+PR+SD at 16 weeks)
Durable Responses in Patients Treated with PLX9486 + Sunitinib • The median duration of PLX9486 + sunitinib treatment was 10 months (range: 1 to 27 months) • Four patients remain on therapy, including 1 CR and 2 PR • Durable response >18 months in patients achieving confirmed response 23 * Patient previously received PLX9486. db snapshot: 10July2020 Durable Responses in Patients Treated with PLX9486 + Sunitinib • The median duration of PLX9486 + sunitinib treatment was 10 months (range: 1 to 27 months) • Four patients remain on therapy, including 1 CR and 2 PR • Durable response >18 months in patients achieving confirmed response 23 * Patient previously received PLX9486. db snapshot: 10July2020
Patient Achieved Complete Response Following Three Prior Therapies When Treated at RP2D of PLX9486 + Sunitinib • 65 yr old female previously refractory to imatinib (PD) and sunitinib (PD); intolerant to regorafenib • Metabolically active right abdominal and subcutaneous masses • Mutation status (ctDNA): KIT exon 11 & 17 • Continues on treatment > 27 months Study Entry PR – Cycle 3 CR – Cycle 18 24Patient Achieved Complete Response Following Three Prior Therapies When Treated at RP2D of PLX9486 + Sunitinib • 65 yr old female previously refractory to imatinib (PD) and sunitinib (PD); intolerant to regorafenib • Metabolically active right abdominal and subcutaneous masses • Mutation status (ctDNA): KIT exon 11 & 17 • Continues on treatment > 27 months Study Entry PR – Cycle 3 CR – Cycle 18 24
PLX9486 Monotherapy Exploratory Analysis: Changes in ctDNA Support Specificity of Kinase Inhibition Patient 1 Patient 2 Months on Treatment Black line: represents average of Sum of Product Diameters 25 Individual lesions represented in colorPLX9486 Monotherapy Exploratory Analysis: Changes in ctDNA Support Specificity of Kinase Inhibition Patient 1 Patient 2 Months on Treatment Black line: represents average of Sum of Product Diameters 25 Individual lesions represented in color
Cogent Biosciences: Emerging Leader in Field of Precision Medicines for Genetically Defined DiseasesCogent Biosciences: Emerging Leader in Field of Precision Medicines for Genetically Defined Diseases
Experienced Leadership Team Cogent’s leadership possesses biotech and large pharma drug development experience and deep scientific expertise in developing precision medicines for genetically defined diseases. ERIN SCHELLHAMMER JESSICA SACHS, M.D. ANDREW ROBBINS BRAD BARNETT JOHN GREEN Chief People Officer Chief Medical Officer Chief Executive Officer & Chief Technology Officer Chief Financial Officer President 27Experienced Leadership Team Cogent’s leadership possesses biotech and large pharma drug development experience and deep scientific expertise in developing precision medicines for genetically defined diseases. ERIN SCHELLHAMMER JESSICA SACHS, M.D. ANDREW ROBBINS BRAD BARNETT JOHN GREEN Chief People Officer Chief Medical Officer Chief Executive Officer & Chief Technology Officer Chief Financial Officer President 27
Financial Overview As of September 30, 2020, Cogent’s current cash balance was $129.4 million. We expect that our current cash will be sufficient to fund our operating expenses and capital expenditure requirements into 2023. Company Capitalization Structure 1 Converted Common Shares As of November 9, 2020 Common stock outstanding 11,342,400 Series A Preferred Stock 40,831,250 Adjusted fully diluted Common stock outstanding 52,173,650 1 This includes 100% conversion of all outstanding Series A Preferred Stock, post 1‐for‐4 reverse split 28Financial Overview As of September 30, 2020, Cogent’s current cash balance was $129.4 million. We expect that our current cash will be sufficient to fund our operating expenses and capital expenditure requirements into 2023. Company Capitalization Structure 1 Converted Common Shares As of November 9, 2020 Common stock outstanding 11,342,400 Series A Preferred Stock 40,831,250 Adjusted fully diluted Common stock outstanding 52,173,650 1 This includes 100% conversion of all outstanding Series A Preferred Stock, post 1‐for‐4 reverse split 28
Current Shareholders Common Shares (1) Preferred Shares (2) (3) Total (Fully Converted) Fairmount Funds Management LLC 1,558,976 16,853,500 18,412,476 Venrock Healthcare Capital Partners 1,088,818 3,409,000 4,497,818 Perceptive Advisors LLC 1,988,750 3,977,500 840,384 2,841,000 3,681,384 Atlas Venture 2,841,000 2,841,000 Acorn Bioventures, L.P. BVF Partners L.P. 2,841,000 2,841,000 Samsara BioCapital, LLC 1,420,455 1,420,500 2,840,955 Logos Global Management LLC 675,000 1,420,500 2,095,500 1,988,750 1,988,750 RTW Investments, LP 1,988,750 1,988,750 OrbiMed Advisors LLC Ridgeback Capital Management, L.P. 600,000 852,250 1,452,250 Ally Bridge Group 1,420,500 1,420,500 Charles Wilson 1,273,779 1,273,779 639,250 639,250 Commodore Capital 625,000 625,000 Polar Capital LLP New Leaf Venture Partners 448,886 448,886 Millennium Management LLC 302,373 302,373 Wedbush Healthcare Partners 2020 Fund, LLC 284,000 284,000 275,794 275,794 Tekla Capital Management LLC 140,774 140,774 The Vanguard Group, Inc. Acuta Capital Partners, LLC 102,500 102,500 100,096 100,096 Fidelity Management & Research Company LLC BlackRock Institutional Trust Company, N.A. 90,091 90,091 Other Investors 1,799,474 1,799,474 Total Share Count 11,342,400 40,831,250 52,173,650 (1) Amounts are based on 13F/D/G filing (2) Preferred Shares are presented on an as converted basis (3) Preferred Shares have been grouped with the underlying Firm where possible 29Current Shareholders Common Shares (1) Preferred Shares (2) (3) Total (Fully Converted) Fairmount Funds Management LLC 1,558,976 16,853,500 18,412,476 Venrock Healthcare Capital Partners 1,088,818 3,409,000 4,497,818 Perceptive Advisors LLC 1,988,750 3,977,500 840,384 2,841,000 3,681,384 Atlas Venture 2,841,000 2,841,000 Acorn Bioventures, L.P. BVF Partners L.P. 2,841,000 2,841,000 Samsara BioCapital, LLC 1,420,455 1,420,500 2,840,955 Logos Global Management LLC 675,000 1,420,500 2,095,500 1,988,750 1,988,750 RTW Investments, LP 1,988,750 1,988,750 OrbiMed Advisors LLC Ridgeback Capital Management, L.P. 600,000 852,250 1,452,250 Ally Bridge Group 1,420,500 1,420,500 Charles Wilson 1,273,779 1,273,779 639,250 639,250 Commodore Capital 625,000 625,000 Polar Capital LLP New Leaf Venture Partners 448,886 448,886 Millennium Management LLC 302,373 302,373 Wedbush Healthcare Partners 2020 Fund, LLC 284,000 284,000 275,794 275,794 Tekla Capital Management LLC 140,774 140,774 The Vanguard Group, Inc. Acuta Capital Partners, LLC 102,500 102,500 100,096 100,096 Fidelity Management & Research Company LLC BlackRock Institutional Trust Company, N.A. 90,091 90,091 Other Investors 1,799,474 1,799,474 Total Share Count 11,342,400 40,831,250 52,173,650 (1) Amounts are based on 13F/D/G filing (2) Preferred Shares are presented on an as converted basis (3) Preferred Shares have been grouped with the underlying Firm where possible 29
Current Analyst Coverage Institution Analyst Jefferies Biren Amin Wedbush David Nierengarten Ladenburg Matt Kaplan 30Current Analyst Coverage Institution Analyst Jefferies Biren Amin Wedbush David Nierengarten Ladenburg Matt Kaplan 30
Thank You CogentBio.com Cogent Biosciences, Inc. | 200 Cambridge Park Drive Suite 2500 | Cambridge, MA 02140 USAThank You CogentBio.com Cogent Biosciences, Inc. | 200 Cambridge Park Drive Suite 2500 | Cambridge, MA 02140 USA