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): January 6, 2021

 

C4 THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

 

 

Registrant’s Telephone Number, Including Area Code: (617) 231-0700

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:

 

Securities registered pursuant to Section 12(b) of the Act:

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

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. ☐

 

 

 

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Item 2.02 Results of Operations and Financial Condition Regulation FD Disclosure

On January 12, 2021, C4 Therapeutics, Inc. (the “Company”) posted a presentation to its website at https://ir.c4therapeutics.com/events-presentations that it expects to share with investors on or before January 14, 2021 in connection with the 39th Annual J.P. Morgan Healthcare Conference. On January 6, 2021, the Company issued a press release announcing its key milestones for 2021. In both the presentation and the press release, the Company disclosed that its unaudited cash, cash equivalents and short-term investments as of December 31, 2020 were approximately $370 million. A copy of the presentation is furnished herewith as Exhibit 99.1 and a copy of the applicable disclosure from the press release is furnished herewith as Exhibit 99.2.

The information contained in Item 2.02 of this Form 8-K is unaudited and preliminary and does not present all information necessary for an understanding of the Company’s financial condition as of December 31, 2020 and its results of operations for the three months and year ended December 31, 2020. The audit of the Company’s consolidated financial statements for the year ended December 31, 2020 is ongoing and could result in changes to the information set forth above.

Item 7.01 Regulation FD Disclosure

The contents of Item 2.02 of this Current Report on Form 8-K are incorporated herein by reference.

The information in this Current Report on Form 8-K, including Exhibits 99.1 and 99.2 attached hereto, is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, nor shall it be deemed subject to the requirements of amended Item 10 of Regulation S-K, nor shall it be deemed incorporated by reference into any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing. The furnishing of this information hereby shall not be deemed an admission as to the materiality of any such information.

Item 9.01 Financial Statements and Exhibits

(d) Exhibits. The exhibits shall be deemed to be filed or furnished, depending on the relevant item requiring such exhibit, in accordance with the provisions of Item 601 of Regulation S-K (17 CFR 229.601) and Instruction B.2 to this form.

 

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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 thereunto duly authorized.

 

 

Corporate Presentation January 2021 Exhibit 99.1

Forward-looking Statements The following presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. These forward-looking statements include, but are not limited to, statements regarding the therapeutic potential of C4 Therapeutics, Inc.’s technology and products. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, as well as the fact that the product candidates that we are developing or may develop may not demonstrate success in clinical trials. Prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. C4 Therapeutics, Inc. undertakes no obligation to update or revise the information contained in this presentation, whether as a result of new information, future events or circumstances or otherwise. Intellectual Property C4 Therapeutics, Inc. owns various registered and unregistered trademarks in the U.S. and overseas, including, without limitation, C4 THERAPEUTICS, TORPEDO, BIDAC and MONODAC. All trademarks or trade names referred to in this presentation that we do not own are the property of their respective owners. Solely for convenience, the trademarks and trade names in this prospectus are referred to without the symbols ® and ™, but those references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. Forward-looking Statements and Intellectual Property 2

z Oncology small molecule therapies generate significant revenue despite known limitations z Targeted Protein Degradation Has the Potential to Transform Treatment of Disease 3 Targeted Protein Degradation Has Potential to Drug the Remaining ~85% of the Human Proteome and Overcome Resistance to Existing Inhibitor Medicines Substantial opportunity to develop treatments for targets previously considered undruggable <15% Of Human Proteome Addressable by Small Molecule Inhibitors $63B 2018 Global Revenue Sources: Hopkins, A., Groom, C. The druggable genome. Nat Rev Drug Discov 1, 727–730 (2002). https://doi.org/10.1038/nrd892; “A view on drug resistance in cancer” Nature | Vol 575 | 14 November 2019; Fact.MR: https://www.factmr.com/report/3747/oncology-small-molecule-drugs-market  z Cancers become resistant to standard therapies and treatment options are then limited Adapted from Wagle et al, J Clin Oncol, 2011 Before 15 weeks 23 weeks POST TREATMENT

C4T is Well Positioned to Develop Targeted Protein Degradation Medicines to Transform Patient Care 4 Strong balance sheet with runway to end of 2023* TORPEDO platform has potential to efficiently design highly potent degrader medicines 4 programs expected in the clinic by end of 2022 14 additional programs in earlier pre-clinical development 3 partnerships expand platform potential; up to $2B in potential milestones *12/31/20 unaudited cash balance of approximately $370M

The Human Body Has A Natural Process to Destroy Unwanted Proteins 5 1 2 3 4

Focus on Overall Catalytic Degradation Targeted Protein Degradation Leverages the Body’s Natural Process to Destroy Disease-Causing Proteins 6

Targeted Protein Degradation Offers Fundamental Advantages Over Protein Inhibition 7 Improved Potency Fast Response High Selectivity Expansive Target Landscape 1 2 3 4

TORPEDO (Target ORiented ProtEin Degrader Optimizer) Platform

Our TORPEDO Platform Has Potential to Efficiently Design Highly Potent Targeted Protein Degrader Medicines Ability to Develop both MonoDACs & BiDACS Focus on Catalytic Efficiency Ability to Design, Analyze & Predict Degrader Performance Investment in Cereblon as E3 Ligase Flexibility to address different targets with tailored approach Optimization of overall degradation process results in maximal efficacy Rapid delivery of potent drug candidates through informed and efficient drug discovery Cereblon is expressed in all tissues and cellular compartments, thereby providing the largest target selection opportunity Benefits Elements 9

TORPEDO Platform Offers Flexibility to Design MonoDACs and BiDACs Flexibility to Address Different Targets with Tailored Approach 10

Enhanced Catalytic Activity Drives Efficacy Improved Catalytic Activity of Degrader A… …Drives Significant Improvement in Target Knockdown 11 Source: C4T data on file

TORPEDO Platform: Robust Drug Discovery Process Enabling Higher Confidence in In Vivo Efficacy Rapid Delivery of Potent Drug Candidates Through Informed and Efficient Drug Discovery 12 Analyze Cellular degradation data fitted using an enzymology framework Key parameters describe intrinsic degradation activity Predict Universal modeling framework merges degradation activity with degrader exposure Robust predictions of depth and duration of in vivo target degradation at any dose Design Computational method incorporates experimental data to identify top models Atomic-level degrader design utilized to improve selectivity and potency

TORPEDO is Based on a Deep Focus on Cereblon, Providing the Largest Target Selection Opportunity  Programs Benefit from Desirable Properties of C4T’s Cereblon Binders  13 Cereblon E3 Ligase Investment in rich toolkit of intellectual property with 14 structurally distinct Cereblon binders Cereblon is expressed in all tissues and in all cellular compartments Cereblon, harnessed by IMiDs, is the only clinically validated ligase for targeted protein degradation C4T’s binders enable drug discovery with enhanced oral bioavailability, solubility, permeability & stability

TORPEDO Platform Has Delivered a Robust Degrader Pipeline; Four Clinical Programs Expected by End of 2022 9 Additional Undisclosed Collaborator Programs in Discovery 14

Three Strategic Target Platform Collaborations Expand Platform Potential 15 4.5-year term beginning January 2019 Focus is on neurological conditions with up to 5 targets total 5-year term beginning March 2017 Focus is on treating diseases of aging, including cancer Signed March 2016 and continues until completion of 6 programs Focus is on oncology treatments targeting a specified set of proteins

IKZF1/3 CFT7455

IKZF1/3: Maximal Catalytic Activity Leads to Improved Efficacy 17 Source: NIH SEER Database, Primary Literature Consensus Patient figures represent estimated U.S. annual incidence PTCL = peripheral T-cell lymphoma; MCL = mantle cell lymphoma Compelling Development Opportunity Potential for accelerated approval in select indications Opportunity to expand into earlier lines of MM therapy Defined Patient Populations MM: ~32K cases/year; median 5-year overall survival (OS): 52% NHL: ~77K cases/year PTCL: ~4% of all NHLs; median 5-year OS: 20-32% MCL: ~7% of all NHLs; median OS: 4-5 years Clear Unmet Need Patients progress on approved IMiD therapies Approved IMiDs have limited activity in NHLs Strong Rationale for Degrader Approach Multiple myeloma (MM) and Non-Hodgkin’s lymphomas (NHLs) are dependent on IKZF1/3 Existing IKZF1/3 degraders have limited potency

CFT7455 Demonstrates Improved Efficacy Compared to Both Approved and Most Advanced Development-stage IKZF1/3 Degraders CFT7455 In Vivo Efficacy – Complete Regression in MM Model CFT7455 In Vivo Efficacy Durable After End of Dosing Period 18 Source: C4T data on file QD Dosing NCI-H929 Tumor Volume (mm3)

CFT7455 Demonstrates Tumor Regression in Multiple Myeloma Xenograft Insensitive to Pomalidomide CFT7455 Active in RPMI-8226, Relative to Pomalidomide CFT7455 Active in RPMI-8226 After Tumor Progression on Pomalidomide Treatment 19 Source: C4T data on file D18

CFT7455 Phase 1/2 Trial Design Offers Potential for Accelerated Approval Across Three Indications IND Submitted December 2020; Trial Expected to Initiate in 1H 2021 20 Phase 1 Dose Escalation R/R Multiple Myeloma Monotherapy N =~30 Cohort B1: R/R Multiple Myeloma Monotherapy N =~12 Cohort C: Non-Hodgkin’s Lymphoma Monotherapy N =~12 Mantle Cell Lymphoma N=~20 Peripheral T-Cell Lymphoma N=~20 Cohort A: Monotherapy(1) R/R Multiple Myeloma (MM) & Non-Hodgkin’s Lymphoma (NHL) N =~6-12 Phase 2 Expansion Cohort B2: R/R Multiple Myeloma Combination with Dexamethasone(2) N =~12 R/R Multiple Myeloma Combo w/ Dexamethasone N =~30 (1) 28-day cycle / dose limiting toxicity (DLT) window; (2) Combination therapy cohorts will open once each CFT7455 dose level has been cleared for safety

BRD9 CFT8634

BRD9: Drugging the Undruggable with a Degrader Approach 22 Source: NIH SEER Database, Primary Literature Consensus Compelling Development Opportunity Well defined path to registration in SS and metastatic population already under management at academic centers Precedent for approval with a single-arm study in second-line setting Defined Patient Populations SS: ~900 cases/year ~10% of all soft tissue sarcomas Clear Unmet Need Very limited benefit of treatments for metastatic or advanced SS – median survival ~18 months Strong Rationale for Degrader Approach Synovial sarcoma (SS) is dependent on BRD9, which is caused by the oncogenic SS18-SSX translocation Oncogenicity of BRD9 depends on sub-domains not addressed by traditional inhibitors Patient figures represent estimated U.S. annual incidence

BRD9 Dependency in Synovial Sarcoma 23 Specifically degrades BRD9 and spares BRD4 and BRD7, avoiding potential off-target toxicities Oncogenicity of BRD9 depends on sub-domains not addressed by traditional inhibitors Advantages of BRD9 degradation Mechanistic Rationale Leveraging a protein degrader approach enables us to effectively target BRD9 since our degraders do not require the binding site to be specifically at the physiologically active domain.

Robust Responses of CFT8634 Seen in Preclinical Synovial Sarcoma Models Dose Response Activity Yamato Xenograft Model Dose Response Activity Patient Derived Xenograft Model 24 IND Submission for CFT8634 Expected in 2H 2021 Source: C4T data on file

BRAF

BRAF: Utilizing a Degrader Approach to Overcome Resistance Mutations 26 Source: NIH SEER Database, Primary Literature Consensus Compelling Development Opportunity Large patient population defined by failure of available BRAF inhibitors Target Population: V600E melanoma and/or NSCLC after failure of MEK inhibitor + BRAF inhibitor with indication specific expansion opportunities Defined Patient Populations >70K annual incidence across melanoma, NSCLC, colorectal cancer (CRC) and other malignancies 50% of late-stage melanoma 1-2% of NSCLC 10-20% of CRC 50% of papillary thyroid cancer 100% of hairy cell leukemia >50% of Langerhans cell histiocytosis (LCH) Clear Unmet Need BRAF mutations occur in ~15% of all cancers ~70% - 90% of BRAF mutations are V600E  Resistance to three approved BRAF inhibitors emerges through multiple paths, resulting in a median PFS of <15 months Strong Rationale for Degrader Approach Approved BRAF inhibitors cause paradoxical RAF activation, which may result in diminished efficacy Potential for degraders to effect deeper elimination of mutant BRAF signaling and create more durable response Patient figures represent estimated U.S. annual incidence BRAF program is partnered with Roche

Advantages of BRAF V600E Degradation Specifically target mutant BRAF over wildtype BRAF Prevent mutant BRAF incorporation into RAF dimers Avoid paradoxical activation and associated failure of therapy due to resistance mechanisms dependent on BRAF inhibitor mediated paradoxical activation BRAF Degrader to Overcome Limitations of Approved BRAF Inhibitors 27 Mechanistic Rationale Inhibitor causes paradoxical activation of wildtype RAF Degrader prevents dimer formation and avoids paradoxical activation BRAF program is partnered with Roche

BRAF Degraders Show Superior Efficacy Compared to Approved BRAF Inhibitors C4T BRAF Degrader Shows More Durable Efficacy Than Encorafenib C4T BRAF Degrader Shows More Durable Efficacy Than Dabrafenib 28 IND Enabling Studies Planned for 2021 Tumor Volume (mm3) Days of Treatment BRAF program is partnered with Roche Source: C4T data on file Vehicle po BID Encorafenib 6 mg/kg PO BID C4T Degrader A C4T Degrader B Vehicle Dabrafenib 100 mg/kg PO QD C4T Degrader C

RET

RET Degradation: Opportunity to Overcome Resistance Mutations 30 Sources: NIH SEER Database, https://pubmed.ncbi.nlm.nih.gov/29284153/, Primary Literature Consensus Compelling Development Opportunity Well defined registration path in existing, genetically defined patient population with no effective treatment option after RET tyrosine kinase inhibition (TKI) Target Population: second line RET-altered cancers; potential for front-line opportunity Defined Patient Populations ~10K annual incidence of RET-driven disease across lung, thyroid, and other cancers 1-2% of NSCLC 60% of sporadic medullary thyroid cancer Clear Unmet Need No effective targeted therapy after failure of approved first-line RET inhibitors Strong Rationale for Degrader Approach RET is a receptor tyrosine kinase (RTK) that plays a role in normal development but can cause cancer when mutated Resistance develops to approved RET inhibitors due to mechanisms including new RET mutations, which make inhibitors inactive Patient figures represent estimated U.S. annual incidence

Mechanistic Rationale RET Degradation May Have Improved Activity Compared to Best-In-Class RET Inhibitors 31 Advantages of RET Degradation RET degrader is active against key secondary mutations that cause resistance, including both the gatekeeper and solvent front mutations Against RET without secondary mutation, as in the front-line setting, degradation may offer deeper and more durable response than inhibition

RET Degrader Has an Excellent Cell Growth Inhibition Profile In RET Fusions and Common Resistance Mutations IND Enabling Studies Planned for 2021 32 KIF5B-RET Fusion Solvent Front Mutation Activating Mutation Drug Naïve, Driver Translocation/Mutation RET Inhibitor Acquired-Resistance Mutants Gatekeeper Mutation Source: C4T data on file

Lead Programs Offer Compelling Opportunities to Address Unmet Need in Multiple Patient Populations  33 Sources: National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Database   MM survival:  https://seer.cancer.gov/archive/csr/1975_2015/browse_csr.php?sectionSEL=18&pageSEL=sect_18_table.08.html#table2.  SS PFS: M. Vlenterie et al. European Journal of Cancer 58 (2016) 62e72; BRAF PFS: Cell Press Review, Trends in Cancer, September 2020, Vol. 6, No. 9; RET PFS: NJEM 383;9 nejm.org 8/27/20 RET BiDAC BRAF BiDAC BRD9 CFT8634 IKZF1/3 CFT7455 6.3 months MEDIAN PFS OF 1L CHEMOTHERAPY 5-year survival 52%  PFS across approved BRAF inhibitors <15 months median PFS ~16.5 months (selpercatinib) Patient figures represent estimated U.S. annual incidence

2021 Milestones Support Progress Toward Goal of Four Clinical-Stage Programs by Year-End 2022 34 IKZF1/3 (CFT7455) BRD9 (CFT8634) BRAF RET Phase 1/2 Initiation IND Submission Phase 1 Top-line Safety & Efficacy Proof of Mechanism Phase 1 Initiation Phase 1 Initiation Phase 1 Initiation IND Enabling Studies IND Enabling Studies

C4T is Well Positioned to Develop Targeted Protein Degradation Medicines to Transform Patient Care 35 Strong balance sheet with runway to end of 2023* TORPEDO platform has potential to efficiently design highly potent degrader medicines 4 programs expected in clinic by end of 2022 14 additional programs in earlier pre-clinical development 3 partnerships expand platform potential; up to $2B in potential milestones *12/31/20 unaudited cash balance of approximately $370M

Thank You

 

Exhibit 99.2

 

Cash Guidance

Unaudited cash, cash equivalents and short-term investments as of December 31, 2020, were approximately $370 million. C4 Therapeutics, Inc. expects its cash, cash equivalents and short-term investments, including payments anticipated to be received under existing collaboration agreements, will be sufficient to fund its operating plan to the end of 2023.

ACTIVE/106555018.1