UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 OR 15(d)
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Date of Report (Date of earliest event reported): October 31, 2023
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Item 7.01. Regulation FD Disclosure.
On October 31, 2023, Context Therapeutics Inc. (the “Company”) issued a press release to announce preclinical data regarding the Company’s preclinical asset, CTIM-76. A copy of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and incorporated herein by reference.
On October 31, 2023, the Company also updated its corporate presentation for use in meetings with investors, analysts and others. A copy of the corporate presentation is filed as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference.
The information in this Item 7.01, and Exhibits 99.1 and 99.2 attached hereto, are being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, regardless of any general incorporation language in such filing.
Item 8.01. Other Events
On October 31, 2023, the Company announced its anticipated filing of an Investigational New Drug Application for CTIM-76 late in the first quarter of 2024.
Item 9.01. Exhibits.
(d) Exhibits
Exhibit No. Description
104 Cover Page Interactive Data File (embedded within the inline XBRL document)
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.
| Dated: October 31, 2023 | Context Therapeutics Inc. | ||||
By: /s/ Martin A. Lehr | |||||
| Name: Martin A. Lehr | |||||
| Title: Chief Executive Officer | |||||
Context Therapeutics Announces Preclinical Data Demonstrating Differentiated and Active Profile of its Claudin 6-Targeted Bispecific Antibody CTIM-76
CTIM-76 exhibits dose-proportional tumor responses and safety in preclinical models
Benchmarking studies comparing CTIM-76 with clinical-stage CLDN6 therapies support CTIM-76's differentiated product profile
CTIM-76 IND filing on track for late Q1 2024
Data to be presented at SITC 38th Annual Meeting on November 3rd
PHILADELPHIA, PA— October 31, 2023—Context Therapeutics Inc. (“Context” or the “Company”) (Nasdaq: CNTX), a biopharmaceutical company advancing medicines for solid tumors, today announced encouraging preclinical data regarding the Company’s preclinical asset, CTIM-76, a Claudin 6 (CLDN6) x CD3 T-cell engaging bispecific antibody.
Findings from Context’s research team, in conjunction with development partner Integral Molecular, illustrate the potential of CTIM-76 to treat CLDN6-positive tumors. Notably:
•CTIM-76 was shown to have high potency and target selectivity in both binding and cytotoxicity assays.
•In in vivo xenograft experiments, CTIM-76 induced dose-proportional tumor regressions and was well tolerated.
•In IND-enabling toxicology studies, CTIM-76 was well tolerated, and a potential first-in-human dose was identified.
•Clones of clinical-stage molecules TORL-1-23 and AMG-794 were generated for benchmarking purposes. In comparison studies, TORL-1-23 activity appeared dependent upon high CLDN6 expression whereas CTIM-76 activity was retained across a range of cell lines expressing with low through high CLDN6. Additionally, CTIM-76 demonstrated ten-fold higher potency than AMG-794 in in vitro cytotoxicity and cytokine activation.
“It is estimated that there are 70,000 patients with CLDN6-positive metastatic solid tumors in the United States, and no approved targeted treatment options exist,” said Martin Lehr, CEO of Context. “We’re encouraged by the promise CTIM-76 has shown with these first in vivo data,
which reinforce the selectivity and potency seen in earlier in vitro data and demonstrate CTIM-76’s ability to induce complete tumor regressions across multiple dose levels. Moreover, our comparison to clones of clinical-stage molecules demonstrates CTIM-76’s ability to address potential target density and toxicity challenges associated with first-generation approaches, as well as highlights CTIM-76’s pharmacologically distinct profile and broad therapeutic potential.”
The data will be presented during a poster session (Abstract #1183) at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting on Friday, November 3, 2023, in San Diego. To view the abstract, visit the SITC meeting website for details.
“The preclinical data at this year's SITC meeting will illustrate the potential of CTIM-76 to target CLDN6,” said Lehr. “We believe these findings collectively support CTIM-76 as a promising
CLDN6-targeting candidate, and we look forward to filing an Investigational New Drug Application late in the first quarter of 2024.”
About Context Therapeutics®
Context Therapeutics Inc. (Nasdaq: CNTX) is a biopharmaceutical company advancing medicines for solid tumors. Context is developing CTIM-76, a selective CLDN6 x CD3 bispecific antibody for CLDN6-positive tumors, currently in preclinical development. CLDN6 is a tight junction membrane protein target expressed in multiple solid tumors, including ovarian, lung, and testicular, and absent from or expressed at low levels in healthy adult tissues. Context is headquartered in Philadelphia. For more information, please visit www.contexttherapeutics.com or follow the Company on Twitter and LinkedIn.
About Integral Molecular
Integral Molecular (integralmolecular.com) is the industry leader in developing and applying innovative technologies that advance the discovery of therapeutics against difficult protein targets. With 20 years of experience focused on membrane proteins and antibodies, Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 500 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, autoimmune disorders, and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue viruses. Follow Integral Molecular on LinkedIn.
Forward-looking Statements
This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are forward-looking statements. These include, without limitation, statements regarding (i) the ability of the Company, its employees and certain SITC presenters to participate in and present at conferences, (ii) the potential benefits, characteristics, and side effect profile of our product candidate, (iii) the likelihood data will support future development, (iv) the ability of our product candidate to have benefits, characteristics, and a side effect profile that is differentiated and/or better than third party product candidates, (v) the likelihood of obtaining regulatory approval of our product candidate, and (vi) our expectation of filing an Investigational New Drug Application for CTIM-76 late in the first quarter of 2024. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we therefore cannot assure you that our plans, intentions, expectations, or strategies will be attained or achieved. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events, or circumstances or otherwise.
This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding strategy, future operations, prospects, plans and objectives of management, including words such as “may,” “will,” “expect,” “anticipate,” “plan,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are forward-looking statements. These include, without limitation, statements regarding (i) the ability of the Company, its employees and certain SITC presenters to participate in and present at conferences, (ii) the potential benefits, characteristics, and side effect profile of our product candidate, (iii) the likelihood data will support future development, (iv) the ability of our product candidate to have benefits, characteristics, and a side effect profile that is differentiated and/or better than third party product candidates, (v) the likelihood of obtaining regulatory approval of our product candidate, and (vi) our expectation of filing an Investigational New Drug Application for CTIM-76 late in the first quarter of 2024. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we therefore cannot assure you that our plans, intentions, expectations, or strategies will be attained or achieved. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events, or circumstances or otherwise.
Media Contact:
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Investor Relations Contact:
Jennifer Minai-Azary
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Context Therapeutics
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November 2023 Corporate Presentation Advancing Medicines for Solid Tumors
Important Notice and Disclaimers Except for statements of historical fact, any information contained in this presentation may be a forward-looking statement that reflects the Company’s current views about future events and are subject to risks, uncertainties, assumptions and changes in circumstances that may cause events or the Company’s actual activities or results to differ significantly from those expressed in any forward-looking statement. In some cases, you can identify forward- looking statements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect”, “estimate”, “anticipate”, “intend”, “goal”, “strategy”, “believe”, “could”, “would”, “potential”, “project”, “continue” and similar expressions and variations thereof. Forward-looking statements may include statements regarding the Company’s business strategy, cash flows and funding status, potential growth opportunities, clinical development activities, the timing and results of preclinical research, clinical trials and potential regulatory approval and commercialization of product candidates. Although the Company believes that the expectations reflected in such forward- looking statements are reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance or achievements. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those described under the heading “Risk Factors” in documents the Company has filed with the SEC. These forward-looking statements speak only as of the date of this presentation and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. 2 Context Therapeutics Inc. - November 2023 Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this Presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. This presentation discusses product candidates that are under preclinical and clinical study, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. While the Company believes its internal research is reliable, such research has not been verified by any independent source. All the scientific, preclinical and clinical data presented within this presentation are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. Forward Looking Statement Company Overview
Lead Program: CTIM-76, a Claudin 6 x CD3 Bispecific Antibody Company Overview 3 CTIM-76 Claudin 6 x CD3 bispecific antibody • Selective for CLDN6: limited off-target effects • Potent: effective CLDN6-positive tumor killing at low doses • Wide therapeutic window: decreased risk of dangerous immune response • IND Filing: on track for late Q1 2024 Context Therapeutics Inc. - November 2023 Opportunity • Claudin 6 (CLDN6) is a tumor-specific protein that is present at high surface density across many adult cancers1 • CLDN6 is expressed at very low levels or absent in normal adult tissue Challenge • CLDN6 antigen is conformationally dependent, which limits access to antibody-antigen binding and antibody development • The CLDN6 antigen binding region is highly conserved with CLDN3, CLDN4, and CLDN9, which increases the risk of off-target binding and potential side effects associated with CLDN3 (pancreas), CLDN4 (liver), and CLDN9 (liver, ear) Target Validation • TORL’s TORL-1-23 ADC and BioNTech’s BNT211 CAR-T cell therapy establishes CLDN6-targeting Proof of Concept2,3: ‒ Efficacy: TORL-1-23 demonstrated 75% ORR (3/4 pts) at 2.4 mg/kg; BNT211 demonstrated 75% ORR (6/8 pts) at DL2 ‒ Safety: TORL-1-23 exhibited MMAE-related toxicities; BNT211 exhibited CRS that was adequately managed with anti-IL6 DL2 = dose level 2; CRS = cytokine release syndrome. 1 Faber MS, et al. Bispecific claudin-6 x CD3 antibodies AACR Annual Meeting; 2021; Virtual. Abstract 1860 , 2 Sahin U, et al. TORL1-23: Initial results of a dose finding Phase 1 study. ASCO 2023; Chicago, IL. Abstract 3082, 3 Haanen JB, et al. BNT211: A Phase I trial. ASCO; 2023; Chicago, IL. Abstract 2518
CTIM-76: Claudin 6 x CD3 Bispecific Antibody Established bispecific format • Highly selective CLDN6 binding fragment antibody-binding (Fab) arm • Immunostimulatory CD3 binding single-chain fragment variable (scFv) domain is designed to be functionally monovalent to avoid aberrant T-cell activation, potentially enhancing safety profile • The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors. A mutation has been inserted into the Fc domain to silence the Fc domain function and avoid T-cell activation by Fc-gamma receptor positive cells Potentially wide therapeutic window • T-cell dependent cellular cytotoxicity with no or minimal activation of circulating cytokines • Humanized CLDN6 and CD3 binding domains Ease of manufacturing • IgG backbone is highly stable and enables high yield Company Overview Context Therapeutics Inc. - November 20234 α-CLDN6 Fab α-CD3 scFv IgG backbone Silenced Fc
Bispecific Antibody T Cell Engagers (bsAb TCE) in Solid Tumors CTIM-76 and other 2nd generation assets are addressing toxicity and dosing challenges associated with 1st generation products Company Overview Context Therapeutics Inc. - November 20235 1 Data as of August 1, 2023 Over 50 TCE in Clinical Development1Innovation Driving Clinical Success Limitations of 1st generation bsAb TCE: 1) Poor pharmacokinetics, continuous dosing 2) Cytokine release syndrome (CRS) 3) On-target/off-tumor toxicity Advantages of 2nd generation bsAb TCE: 1) Potential for dosing every 1-3 weeks 2) Improved TCE engineering to mitigate CRS 3) Better target selection and/or enhanced avidity 0 1 2 3 4 5 6 7 8 TROP2 B7H3 CLDN6 CLDN18.2 PSMA EGFR DLL3 HER2 CEA EpCAM Clinical Assets per Target Select Assets in Clinical Development
Claudin-targeted Therapeutics are Gaining Momentum $263 million raised in 2023 for early-stage programs from TORL and Alentis Company Overview TORL Biotherapeutics (Private) Alentis Therapeutics (Private) Description Funding to advance TORL-1-23, a first-in-class, clinical- stage ADC targeting Claudin 6 and other novel clinical and preclinical stage programs. $158 million Financing Participating Investors Description Funding to advance clinical programs ALE.F02 and ALE.C04 – two first-in-class anti-Claudin-1 (CLDN1) antibodies for organ fibrosis and CLDN1 positive tumors. $105 million Financing Participating Investors Selected information presented is for illustrative purposes only6 Context Therapeutics Inc. - November 2023
Claudin-targeted Therapeutics are Gaining Momentum Internal and competitor milestones Company Overview Internal Milestone Competitor Milestones 7 November: CTIM-76 preclinical update at SITC conference Q1 2024: CTIM-76 IND filing October: TORL Biotherapeutics TORL-1-23 Phase 1 data update at ESMO conference October: BioNTech BNT211 Phase 1 data update (Late-Breaker) at ESMO conference November: Chugai SAIL66 preclinical update at SITC conference Context Therapeutics Inc. - November 2023
Claudin 6 (CLDN6) Target biology and therapeutic rationale Context Therapeutics Inc. - November 20238
CLDN6 is an Oncofetal Protein Oncofetal proteins are considered favorable candidates for immunotherapy • Normally present at higher levels during embryonic development • Turned off or have low levels of expression in adult tissues • Increased expression known to occur in some tumor cells, including non-small cell lung cancer (NSCLC), ovarian, and testicular CLDN6 Target Biology Context Therapeutics Inc. - November 20239 Oncofetal Characteristics of CLDN6 Huan, Mol Med Reports, 2021
CLDN6 Has the Potential to Reach a Large Patient Population ~70,000 patients per year in the US only in Relapse/Refractory Setting CLDN6 Target Biology 10 Selected Cancer indications Incidence R/R Incidence CLDN6 Positive Patient Population Based on R/R Incidence Non-Small Cell Lung 201,229 110,653 6-50%3,4,5 35,221 Ovarian 19,900 12,800 91%14 11,648 Testicular 9,910 400 100%14 400 Breast 290,600 43,800 2-41%1,10,11 9,417 Gastric 26,380 11,090 13-55%8,9 3,771 Endometrial 65,900 12,500 20-31%1,12,13 3,188 Sarcoma 17,100 12,390 20%14 2,478 Glioma 19,000 10,000 21%8 2,100 Bladder 81,180 17,100 2-8%1,13 855 Small Cell Lung 35,511 19,527 2%1 391 Malignant Rhabdoid 50 500 29-44%1,2,6,7 183 1 Reinhard, Science, 2020; 2 Wang, Diagn Pathol., 2013; 3 Gao, Oncol Lett., 2013; 4 Kohmoto, Gastric Cancer, 2020; 5 Lin, Diagn Pathol., 2013; 6 Micke, Intl J Cancer, 2014; 7 Soini, Pol J Path, 2022; 8 Antonelli, Brain Pathol., 2011; 9 Sullivan, Am J Surg Pathol., 2012; 10 Jia, Intl J Clin Exp Pathol., 2019; 11 Yafang, J Breast Cancer, 2011; 12 Kojima, Cancers, 2020; 13 Ushiku, Histopath., 2012; 14 Mackensen, Nature Medicine, 2023. Incidences based on public estimates; Relapsed/refractory (R/R) or last-line patient population approximated by annual mortality; CLDN6 target prevalence is based on IHC or RNAseq from published reports. Patient population derived from midpoint of CLDN6 positive population multiplied by R/R incident population. Initial indications of interest based on: • CLDN6 prevalence • Patient population size • Observed clinical responses • Eligibility for Orphan Designation Context Therapeutics Inc. - November 2023
CLDN6 is Selectively Expressed on Cancer Cells CLDN6 Target Biology Context Therapeutics Inc. - November 202311 (a) adrenal gland, (b) fallopian tube, (c) kidney, (d) liver, (e) thyroid, (f) prostate, (g) esophagus, (h) stomach, (i) colon, (j) cerebrum, (k) cerebellum, (l) spinal cord. (m) thymus, (n) spleen, (o) bone marrow, (p) pancreas, (q) skin, (r) bladder, (s) placenta, (t) heart muscle, (u) striated muscle, (v) testis, (w) ovary, (x) lung (CA1) testicular cancer, (CA2) ovarian cancer, and (CA3) lung cancer Reinhard, Science, 2020 Normal TissueCancer Tissue
High CLDN6 Associated with a Worsened Prognosis in Cancer Patients CLDN6 Target Biology Context Therapeutics Inc. - November 202312 Endometrial Cancer1 Overexpression of CLDN6 is associated with worse overall survival in endometrial cancer patients 1 Kojima, Cancers, 2020; 2 Zhang, Front. Cell Dev. Biol., 2021; 3 Kohmoto, Gastric Cancer, 2020 Bladder Cancer2 Overexpression of CLDN6 is associated with worse overall survival and higher disease stage (more aggressive) in bladder cancer patients Stomach Cancer3 Overexpression of CLDN6 is associated with worse overall survival in stomach cancer patients
CLDN6 Has Limited Overlap with Competing Drug Targets in Solid Tumors CLDN6 Target Biology Context Therapeutics Inc. - November 202313 Bishop, AnalyzeR [Data Set] Accessed August 1, 2023 CLDN6 vs. TROP2 CLDN6 vs. NECTIN4 Respiratory Cancer Limited correlation with TROP2 and Nectin-4, no correlation with PD-L1 and EGFR Female Reproductive Cancer Limited correlation with PD-L1 and MUC16, no correlation with Mesothelin and Folate Receptor Alpha CLDN6 vs. PD-L1 CLDN6 vs. EGFR CLDN6 vs. PD-L1 CLDN6 vs. MUC16 CLDN6 vs. Mesothelin CLDN6 vs. Folate Receptor
CTIM-76 Claudin 6 x CD3 Development Candidate Context Therapeutics Inc. - November 202314
Developing a Highly Selective CLDN6 Antibody is Challenging CTIM-76 Program Context Therapeutics Inc. - November 202315 CLDN9 CLDN6 CLDN4 CLDN3 CLDN5 CLDN8 CLDN17 CLDN2 CLDN14 CLDN20 CLDN7 CLDN1 CLDN19 CLDN34 CLDN12 CLDN23 CLDN16 CLDN24 CLDN22 CLDN25 CLDN18 CLDN11 CLDN15 CLDN10 • CLDN6 antigen is conformationally dependent, which limits access to antibody-antigen binding • Antigen binding region is highly conserved with CLDN3, CLDN4, and CLDN9, making CLDN6- selective binding a challenge1 • CLDN6 selectivity is required to avoid off-target liabilities identified in murine knockout and knockdown studies with CLDN3 (intestine)2, CLDN4 (liver, pancreas)3, and CLDN9 (liver, ear)4 1 Screnci, Cancer Res, 2022; 2 Tanaka, J Hepatol, 2018; 3 Cordat, Physiology, 2019; Li, FEBS Open Bio, 2020; 4 Nakano, PLoS Genet, 2009 Human CLDN Family Tree
CTIM-76 Exhibits Excellent Selectivity and Potency CTIM-76 Program Context Therapeutics Inc. - November 202316 • CTIM-76 CLDN6 EC50 of 3.41 nM (binding) • CTIM-76 preferentially binds to CLDN6 over CLDN3/4/9 • CLDN3/4/6/9 were transiently transfected in HEK-293F cells (4:1 Target:GFP) CLDN6 Selectivity -11 -10 -9 -8 -7 -6 -5 0 50,000 100,000 150,000 200,000 Log [Bispecific] (M) Ce ll Bi nd in g (M FI ) Human CLDN6 Human CLDN4 Human CLDN3 Human CLDN9 Negative CLDN6 Potency • Potency assay provides a better assessment than binding assays for off-target liabilities associated with CLDN3, CLDN4, or CLDN9 • CTIM-76 CLDN6 EC50 of 0.0004 nM (cytotoxicity) • CTIM-76 preferentially targets CLDN6, with minimal binding and cytotoxicity against CLDN9-expressing cells >10,000x >500x
CTIM-76 Induces Specific Lysis CTIM-76 showed potent and specific killing of even those cell lines with very low CLDN6 expression Context Therapeutics Inc. - November 202317 K562-CLDN6 OV90 HEK CLDN6 Expression High Medium Low CTIM-76 (EC50) 0.0004 nM 0.049 nM 2.79 nM OV90 Cell LineK562-CLDN6 Cell Line HEK Cell Line -4 -3 -2 -1 0 0 50 100 Log [bsAb] (nM) % S pe ci fic C yt ot ox ic ity CTIM-76 Negative Ctrl -4 -2 0 2 4 -50 0 50 100 Log [bsAb] (nM) % S pe cif ic Cy to to xic ity -4 -2 0 2 4 -50 0 50 100 Log [bsAb] (nM) % S pe cif ic Cy to to xic ity CTIM-76 Negative Ctrl CTIM-76 Negative Ctrl CTIM-76 Program
CTIM-76 Program Context Therapeutics Inc. - November 202318 CTIM-76 Exhibits Limited Activation of Free Cytokines • Data supports potential to dose at levels that promote cancer cell killing but have manageable levels of free cytokine production, thereby potentially reducing the risk of cytokine release syndrome • Cytokine production evaluated in exogenous (CLDN6-K562) cell line model at 48 hours • Cytokine production happens well above the concentration of maximal killing (TDCC EC50 = 0.0004 nM) CTIM-76 Cytokine Control % Lysis CTIM-76 % Lysis TDCC vs IL2 -4 -3 -2 -1 0 -50000 0 50000 100000 150000 0 20 40 60 80 100 Log [bsAb] (nM) pg /m L % Specific Cytotoxicity EC50 TDCC vs IFNg EC50 -4 -3 -2 -1 0 -50000 0 50000 100000 150000 0 20 40 60 80 100 Log [bsAb] (nM) pg /m L % Specific Cytotoxicity TDCC vs TNFα EC50 -4 -3 -2 -1 0 -500 0 500 1000 0 20 40 60 80 100 Log [bsAb] (nM) pg /m L % Specific Cytotoxicity TDCC vs IL10 EC50 -4 -3 -2 -1 0 -50 0 50 100 150 0 20 40 60 80 100 Log [bsAb] (nM) pg /m L % Specific Cytotoxicity Study Design: K562 cells stably over-expressing CLDN6 and luciferase were co-cultured with human T cells at an E:T ratio of 10:1 for 48 hours. Cytotoxicity was determined by luminescence imaging. CTIM-76 Cytokine Control % Lysis CTIM-76 % Lysis CTIM-76 Cytokine Control % Lysis CTIM-76 % Lysis CTIM-76 Cytokine Control % Lysis CTIM-76 % Lysis Comparison of T cell-dependent cellular cytotoxicity (TDCC) to Cytokine Production >100x >100x >100x ~100x
CTIM-76 Inhibits Tumor Growth in a Mouse Xenograft Model CTIM-76 Program Context Therapeutics Inc. - November 202319 CTIM-76 induced regression of established subcutaneous OVCAR3 xenograft tumors • CTIM-76 effectively engaged systemically administered human PBMC cells to promote significant tumor regression and complete responses in OVCAR3 ovarian xenograft models in mice • NSG-b2m knockout mice (n=14/arm) engrafted with human PBMCs and bearing advanced subcutaneous OVCAR3 tumor xenografts (~150,000 CLDN6 copies per cell) were treated twice per week with vehicle or CTIM-76 Efficacy Tolerability NSG: NOD scid gamma immunodeficient mice; PBMC: peripheral blood mononuclear cells • CTIM-76 was well tolerated in OVCAR3 xenograft study 0 150 300 450 600 0 7 14 21 Tu m or V ol um e (m m 3) Day Vehicle 0.01mg/kg 0.1mg/kg 1.0mg/kg 18 20 22 24 26 28 0 7 14 21 G ra m s Day Vehicle 0.01mg/kg 0.1mg/kg 1.0mg/kg Tumor Regression Well tolerated
CTIM-76 Program CTIM-76 was well tolerated in Toxicology Study in Cynomolgus Monkeys Context Therapeutics Inc. - November 202320 CTIM-76 is Cross-Reactive to Cynomolgus Monkey CLDN6 and CD3 ̶ Exhibited linear pharmacokinetics ̶ Supports weekly dosing in Phase 1 study ̶ Cmin above threshold required for therapeutic activity CTIM-76 was well tolerated in Toxicology Study in Cynomolgus Monkey: ̶ well tolerated at projected therapeutic doses ̶ No major CRS-associated clinical symptoms or toxicity ̶ CLDN4/9 hepatobiliary effects were generally mild Pharmacokinetics After Second Dose (Day 8) OVCAR3 Activity Threshold
Competitive Landscape 21 Context Therapeutics Inc. - November 2023
Few CLDN6 Programs Have Excellent CLDN6-Selectivity CTIM-76, TORL-1-23, and AMG-794 are selective for CLDN6 vs CLDN3, CLDN4, CLDN9 Competitive Landscape Context Therapeutics Inc. - November 202322 HEK-293F cells were transfected with human CLDN6, CLDN9, CLDN3, or CLDN4 and stained with the indicated concentration of TORL ADC, Amgen BiTE, or CTIM-76. TORL ADC Amgen BiTE CTIM-76 • Clones of TORL-1-23 and AMG-794 were generated by Context for benchmarking purposes ̶ The clones are not derived from the original manufacturer and were produced for this research study based on the published sequence of their antibody variable chains, thus, the clones used in this study are biosimilars and may not be identical to the MAbs formulated for clinical development • TORL-1-23 ̶ A clinical-stage CLDN6 antibody-drug conjugate (ADC) that incorporates a protease-labile linker and an MMAE payload ̶ TORL-1-23 clone (“TORL ADC”) was generated from CLDN6 antibody AB3-7 (WO2020/191342) with MMAE conjugated using AlphaThera’s oYo link system with a 2:1 drug-antibody ratio • AMG-794 ̶ A clinical-stage T cell engaging bispecific antibody that incorporates a BiTE® conjugated to an Fc domain to achieve half-life extension (HLE) ̶ AMG-794 clone (“Amgen BiTE”) was generated from CLDN6 antibody SEQ ID No: 21 (WO2022/096700) and conjugated to an Fc domain for HLE CLDN6 CD3 CLDN6 CD3 CLDN6 CLDN6
Competitive Landscape TORL ADC Internalization Restricted to Cells with High Levels of CLDN6 Context Therapeutics Inc. - November 202323 • TORL-1-23MAb internalizes in a cell line where CLDN6 is overexpressed • TORL-1-23MAb does not internalize in a cell line with moderate CLDN6 expression • TORL-1-23 is potentially best utilized in tumors with high levels of CLDN6 expression where the ADC can bathe the tumor, thereby enhancing the probability of a tumor response and decreasing the level of free MMAE in plasma High CLDN6 (K562-CLDN6) Moderate CLDN6 (OV90) TORL-1-23 clones are not derived from the original manufacturer and were produced for this research study based on the published sequence of their antibody variable chains, thus, the clones used in this study are biosimilars and may not be identical to the MAbs formulated for clinical development. Monoclonal antibody (mAb) variant of TORL-1-23 was generated (TORL-1-23MAb) for benchmarking purposes from CLDN6 antibody AB3-7 (WO2020/191342). Antibodies were labeled with a pH-sensitive dye, pHrodo, using pHrodo iFL Red Microscale Protein Labeling Kit (Thermo Fisher Scientific) and incubated in OV90 ovarian cancer cells for 2 hours and 24 hours (data not shown) TORL-1-23MAb CTIM-76 Control
TORL ADC Potency Requires High Levels of CLDN6 Competitive Landscape Context Therapeutics Inc. - November 202324 • TORL ADC may be best utilized in cancers that express high levels of CLDN6, including testicular and ovarian cancers • TORL ADC incorporates a functional Fc and is active in cells with moderate CLDN6 expression only when immune cells are present • TORL-1-23 activity is likely derived primarily from ADC internalization and/or bystander killing in high CLDN6 cells and to a lesser extent from complement-mediated immune activation due to a functional Fc domain High CLDN6 (K562-CLDN6) Moderate CLDN6 (OV90) TORL ADC CTIM-76 TORL ADC CTIM-76
-14 -12 -10 -8 -6 0 2,000 4,000 6,000 8,000 Log [bsAb] (M) [C yt ok in e] (p g/ m L) CTIM-76 is a More Potent Inducer of Cytotoxicity and T Cell Activation than AMG-794 Competitive Landscape Cytotoxicity in OV90 Cell Line Cytokine Activation IL-6 at 24 Hours 25 1 Pham et al, AMG-794, a Claudin 6-targeted half-life extended (HLE) bispecific T cell engager (BITE®) , AACR 2022; 2 Amgen Patent WO2022096700 • AMG-794 is a BiTE that incorporates a detuned CD3 (standard for BiTEs) and an Fc domain for half-life extension (HLE-BiTE) • AMG-794 has exhibited dose-limiting side effects in murine and cynomolgus monkey studies1,2 • CTIM-76 is ~10x more potent than Amgen BiTE in in vitro cytotoxicity and cytokine activation assays 12.5:1 Effector:Target - 1 4 - 1 2 - 1 0 - 8 - 6 - 5 0 0 5 0 1 0 0 Log [bsAb] (M) % S pe ci fic C yt ot ox ic ity CTIM-76 Amgen BiTE Vertical lines represent cytotoxicity EC50 CTIM-76 Amgen BiTE Percent Weight Loss in Xenograft1,2 1 mg/kg Dose in OVCAR3 -25 -20 -15 -10 -5 0 CTIM-76 AMG-794 Context Therapeutics Inc. - November 2023
BNT211 and TORL-1-23 Phase 1 Data at ESMO 2023 and ASCO 2023 Competitive Landscape Context Therapeutics Inc. - November 202326 BNT211 TORL-1-23 Conference ASCO ESMO ASCO ESMO Cutoff Date March 10, 2023 September 10, 2023 May 3, 2023 September 29, 2023 Patients (n) 19 (17 evaluable) Ovarian = 8 Testicular = 6 Lung = 1 Other = 4 44 (38 evaluable) Ovarian = 17 Testicular = 16 Other =11 (4 lung, 3 round cell, 2 esophageal, 1 endometrial, 1 sinonasal) 25 Ovarian = 19 Testicular = 3 Endometrial = 3 42 (36 evaluable) 17 pts at 3 mg/kg Ovarian = 30 Testicular = 5 Endometrial = 7 Median Prior Treatments, n (range) 4 (2-9) 4 (2-9) 5 (1-10) 4 (1-9) ORR, n (%) Overall: 41% (7/17) Dose Level 0 or 1: 11% (1/9) Dose Level 2: 75% (6/8) Ovarian DL2: 80% (4/5) Overall: 44% (17/38) Dose Level 0 or 1: 11% (1/9) Dose Level 2: 59% (13/22) Ovarian DL2: 77% (7/9) Testicular DL2: 38% (3/8) Other DL2: 60% (3/5) Overall: 28% (7/25) Ovarian: 32% (6/19) Ovarian, 2.4mg/kg: 75% (3/4) Overall: 31% (11/36) Ovarian: 33% (9/27) Other: 22% (2/9) Ovarian, ≥2.4mg/kg: 50% (6/12) SAE Grade 3: sepsis (1 pt) Grade 4: CRS (1pt @ DL3) Grade 5: sepsis (1 pt) Grade 4: lymphocytopenia (1 pt) Grade 5: pneumonia (1 pt) Grade 4: blood counts at higher doses Grade 5: pneumonia (1 pt) Treatment-Related AEs LFT Blood counts LFT Bilirubin Alopecia Anemia Neuropathy Pneumonia Alopecia Anemia Neuropathy Pneumonia
CLDN6 Competitive Landscape1 Context Therapeutics Inc. - November 202327 Scalable Manufacturing Process Complex Manufacturing Process Potential / Disclosed Safety Liabilities Selectivity for CLDN6 vs CLDN3,4,9 Limited Information on Asset Limited Selectivity Deprioritized CLDN6-CAR-NK CAR-NK + IL7 FPI Q2 22 TJ-C64B2 2+2 bsAb CLDN6x4IBB TORL-1-23 CLDN6 + MMAE FPI Q4 21 SAIL66 bsAb CLDN6xCD3 FPI Q1 23 1 Analysis based on current understanding of publicly available information compiled as of October 23, 2023 and internal benchmarking studies; 2 TJ- C64B deprioritization per Q2 2023 earnings guidance; 3 Pham et al, AMG 794, a Claudin 6-targeted half-life extended (HLE) bispecific T cell engager (BITE®), AACR 2022; 4 Hamilton, First-in-human study of SC-004, AACR 2020; FPI = First Patient In Phase 1 trial; DLT = Dose Limiting Toxicity CTIM-76 bsAb CLDN6xCD3 IND Q1 24 Competitive Landscape Undisclosed CAR-NK IND 2H 23 Undisclosed bsAb CLDN6xCD3 IND Q4 23 BNT211 CAR-T + CARVac FPI Q3 20 AMG-7943 BiTE CLDN6xCD3 FPI Q1 23 BNT142 mRNA BsAb CLDN6xCD3 FPI Q1 22 XmAb541 2+1 bsAb CLDN6xCD3 IND 2H 23 DS-9606a CLDN6/CLDN9 + 2nd gen toxin FPI Q2 22 GB-7008-01 CLDN6/CLDN9 + MMAE Status Unknown Selective, Potent, Scalable SC0044 CLDN6/CLDN9 + PBD Ph 1 DLT
Corporate 28 Context Therapeutics Inc. - November 2023
Corporate Experienced Leadership Team • Experienced team with deep oncology experience • Our CMO led the clinical development of multiple blockbuster drugs including Kisqali, Arimidex, and Afinitor • Our management team is supported by a Board with strong public company operating and governance experience Focus on Execution Martin Lehr CEO and Director Tarek Sahmoud, MD, PhD Chief Medical Officer Alex Levit, Esq Chief Legal Officer Jennifer Minai, CPA Chief Financial Officer Chris Beck, MBA SVP Operations Priya Marreddy, MS VP Clinical Operations Context Therapeutics Inc. - November 202329
Corporate Investment Highlights (Nasdaq: CNTX) Solid Tumors Large Unmet Need Claudin 6 High-Value Target November SITC Poster Anticipated Late Q1 2024 IND filing Milestones Deep Domain Experience, Track Record of Success Strong Team Expected Cash Runway into late 2024 Financial Strength Context Therapeutics Inc. - November 202330
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