UNITED STATES
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FORM
CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On December 16, 2021, Cullinan Oncology, Inc. (the “Company”) issued a press release reporting updated data from the Company’s ongoing Phase 1/2a trial of CLN-081 in non-small cell lung cancer patients whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations that have progressed on or after prior therapy, a copy of which is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K.
In addition, the Company has made available on its website the Company’s presentation from the 2021 Cullinan Oncology Clinical Data Report Virtual Webcast. The presentation has been added to the “Events” section of the Company’s website at https://investors.cullinanoncology.com. A copy of the presentation is furnished herewith as Exhibit 99.2 to this Current Report on Form 8-K.
The information in this Item 7.01, including Exhibits 99.1 and 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for 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, except as expressly set forth by specific reference in such filing.
| Item 9.01. | Exhibits |
| Exhibits | ||
| 99.1 | Press release issued by Cullinan Oncology, Inc. on December 16, 2021, furnished herewith. | |
| 99.2 | 2021 Cullinan Oncology Clinical Data Report Virtual Webcast Presentation, dated December 2021, furnished herewith. | |
| 104 | Cover page from this Current Report on Form 8-K, formatted in Inline XBRL | |
SIGNATURE
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.
| CULLINAN ONCOLOGY, INC. | ||||
| Dated: December 16, 2021 | By: | /s/ Jeffrey Trigilio | ||
| Jeffrey Trigilio | ||||
| Chief Financial Officer | ||||
Exhibit 99.1
Cullinan Oncology Announces Updated Phase 1/2a Data for
CLN-081 in NSCLC EGFR Exon 20 Patients
CLN-081 continues to demonstrate a differentiated clinical profile at the recommended Phase 2 dose of 100mg BID
Continued high response rate with favorable safety and tolerability profile observed in heavily pre-treated patients at 100mg BID
Encouraging durable responses and progression free survival at 100mg BID
Cambridge, MA, December 16, 2021 – Cullinan Oncology, Inc. (Nasdaq: CGEM) (“Cullinan”), a biopharmaceutical company focused on developing a diversified pipeline of targeted therapies for cancer patients, today reported updated data from the Company’s ongoing Phase 1/2a trial of CLN-081 in non-small cell lung cancer (NSCLC) patients whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations that have progressed on or after prior therapy.
“The updated data from our ongoing Phase 1/2a study in a larger number of patients further reinforce CLN-081’s differentiated clinical profile. CLN-081 has demonstrated both a high response rate and durable responses in heavily pre-treated patients,” said Nadim Ahmed, Chief Executive Officer of Cullinan Oncology. “For many lung cancer patients currently receiving EGFR inhibitors, treatment related side effects can significantly impact their daily lives. In this regard, we are encouraged by CLN-081’s favorable safety profile at the 100mg BID dose.”
The current analysis of the ongoing trial included a total of 73 NSCLC patients with EGFR exon 20 insertion mutations who received at least one dose of CLN-081 and were evaluable for safety as of the data cutoff. CLN-081 was administered orally, at dose levels including 30, 45, 65, 100 and 150 mg twice daily (BID). Based on prespecified safety and efficacy criteria, enrollment at the Phase 2a cohort for 100mg BID was expanded up to the planned maximum of 36 patients. Additional patients were also enrolled at the 150mg BID dose level, although enrollment was subsequently discontinued after a total of 11 patients based on overall assessment of the clinical profile at this dose level. Guided by these data,100mg BID was nominated as the Recommended Phase 2 Dose (RP2D) for CLN-081.
Efficacy Highlights:
Efficacy data from patients enrolled in the 100mg BID cohort:
| • | Of 36 response evaluable patients, 14 achieved a confirmed PR for a 39% confirmed response rate and one additional patient had a PR that was pending confirmation at the time of the data cut-off. |
| • | The median duration of response was >15 months and the median progression free survival was 12 months in the initial cohort of phase 1 patients (N=13). |
Safety and Tolerability Highlights:
Treatment related EGFR associated adverse event (AE) data for patients enrolled in the 100mg BID cohort:
| • | Rash has been limited to Grade 1 and 2 events (54% and 18% of patients, respectively). Events were manageable with conventional supportive care and no patients have experienced Grade 3 or greater treatment-related rash. |
| • | Diarrhea has been limited to Grade 1 and 2 events (26% and 8% of patients, respectively). No prophylactic regimen has been required to ameliorate the incidence or severity of diarrhea to date, and no patients have experienced Grade 3 or greater treatment-related diarrhea. |
“We are pleased with CLN-081’s safety and efficacy to date. CLN-081 has demonstrated antitumor activity among heavily pre-treated patients, including patients treated previously with other EGFR inhibitors or immunotherapy, and across a spectrum of exon 20 mutational sub-types,” said Jon Wigginton, M.D., Chairman of the Cullinan Oncology Scientific Advisory Board and Senior Advisor. “We are similarly encouraged by the emerging durability data shown in this update, which we believe could also reflect the benefit of the drug’s favorable safety and tolerability profile. Our goal now is to review these results and potential future clinical development with the FDA and to move CLN-081 as expeditiously as possible into late-stage development.”
Additional data are available in a presentation accompanying this press release on the Events section of our website.
About CLN-081
CLN-081 is an orally available, irreversible EGFR inhibitor that selectively targets cells expressing EGFR exon 20 insertion mutations while sparing cells expressing wild type EGFR. Cullinan is evaluating various doses of CLN-081 in a Phase 1/2a trial in patients with NSCLC harboring exon 20 mutations whose disease has progressed on or after prior therapy.
About Cullinan Oncology
Cullinan Oncology is a biopharmaceutical company that is developing a diversified pipeline of targeted therapeutic candidates across multiple modalities in order to bring important medicines to cancer patients. The Company’s strategy is to source innovation through both internal discovery efforts and external collaborations, focusing on advanced stage assets with novel technology platforms and differentiated mechanisms. Learn more about Cullinan at www.cullinanoncology.com.
Forward-Looking Statements
This press release contains forward-looking statements of Cullinan Oncology, Inc. (“Cullinan,” “we” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Cullinan’s beliefs and expectations regarding our preclinical and clinical development plans, clinical trial designs, clinical and therapeutic potential, and strategy of our product candidates, including but not limited to our expectations and beliefs around the safety and activity of CLN-081. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of
future events, and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; success of our clinical trials and preclinical studies; risks related to our ability to protect and maintain our intellectual property position; risks related to manufacturing, supply, and distribution of our therapeutic candidates; risks related to the impact of COVID-19 affecting countries or regions in which we have operations or do business, including potential negative impacts on our employees, customers, supply chain and production as well as global economies and financial markets; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, or SEC, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither Cullinan nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.
Contacts:
Investor Relations
Lee Roth / Dr. Grace Kim
+1 212.213.0006
Lroth@burnsmc.com / gkim@burnsmc.com
Jeffrey Trigilio
+1 617.410.4650
jtrigilio@cullinanoncology.com
Media
Ariane Lovell
+1 917.565.2204
ariane.lovell@finnpartners.com
Exhibit 99.2 Mining for Tomorrow’s Cures CLN-081 Clinical Update December 2021
Important Notice and Disclaimers This presentation contains forward-looking statements of Cullinan Oncology, Inc. (“Cullinan,” “we” or “our”). These forward-looking statements include, but are not limited to, express or implied statements regarding Cullinan’s beliefs and expectations regarding our preclinical and clinical development plans, clinical trial designs, clinical and therapeutic potential, and strategy of our product candidates, including but not limited to statements concerning the safety and efficacy of CLN-081, development plans for CLN-081 and the potential therapeutic benefits of CLN-081. Any forward- looking statements in this presentation are based on management's current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; success of our clinical trials and preclinical studies; risks related to our ability to protect and maintain our intellectual property position; risks related to manufacturing, supply, and distribution of our therapeutic candidates; risks related to the impact of COVID-19 affecting countries or regions in which we have operations or do business, including potential negative impacts on our employees, customers, supply chain and production as well as global economies and financial markets; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, or SEC, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-Q and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so except as required by law, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation. Moreover, except as required by law, neither Cullinan nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this presentation. 2
Executive hosts of today’s webinar Nadim Ahmed Jon Wigginton, MD Chief Executive Officer Senior Advisor & Chairman of SAB Leigh Zawel, PhD Jeff Trigilio Chief Scientific Officer, Chief Financial Officer Small Molecules 3
Cullinan Oncology: Advancing a broad pipeline of targeted cancer therapeutics Discovery / IND- Program (Subsidiary/Project) Lead Phase 1 Phase 2 Phase 3 Enabling Modality / MOA Optimization CLN-081 (Pearl) NSCLC EGFRex20 EGFR ex20 inhibitor ➢ Strategy to select programs with CLN-049 (Florentine) r / r AML FLT3 x CD3 bispecific First and/or Best in Class Potential CLN-619 (MICA) ➢ Q4 Progress: Pan cancer Anti-MICA/B IgG1 ✓ CLN-081 clinical update CLN-978 (NexGem) B-cell ALL CD19, CD3, HSA trispecific ✓ FLT3 trial initiation CLN-617 (Amber) ✓ MICA trial initiation Pan cancer IL2-IL12 fusion protein ➢ Further pipeline updates to come Pan Opal in early 2022 cancer PD-1 x CD137L fusion protein Jade HPV+/ TCR-based therapy targeting a novel RB- senescence / cancer-related protein 4
CLN-081 Clinical update highlights Data Summary Status Efficacy Safety ▪ High response rate in ▪ Nominated RP2D of ▪ Favorable safety and larger number of patients 100mg BID tolerability profile ▪ Durable responses and encouraging PFS CLN-081: A differentiated clinical profile 5
CLN-081: Selective EGFR inhibitor for NSCLC patients with exon 20 mutations CLN-081: Unique design properties Select CLN-081 pre-clinical data Selectivity Index IC50 WT/mutant LXF2478 PDX model for lung cancer High harboring EGFR V769_D770INSASV Distinct selectivity chemical HER2- to mutant scaffold sparing vs WT EGFR 6
CLN-081 Phase 1/2a trial design Patient Enrollment Accelerated Phase 1 Phase 2a Dose (BID) Rolling 6 Titration Expansion Expansion N = 2 N = 6 30 mg ➢ 36 patients enrolled in Phase 1/2a at 100 mg BID N = 1 45 mg ➢ Expanded enrollment at 150 mg BID stopped after N = 1 N = 6 N = 7 65 mg 11 patients based on clinical profile N = 1 N = 6 N = 6 N = 23 100 mg ➢ Dose of 100 mg BID nominated as RP2D N = 7 N = 4 150 mg Geographic Footprint US Netherlands Singapore Hong Kong Taiwan China Location IND Zai Lab has licensed CLN- 9 1 2 1 1 # of Sites approved 081 for Greater China. 7 Clinical data cutoff as of 1 Dec 2021
Heavily pretreated patient population including prior EGFR TKI or immunotherapy Select Baseline Characteristics Characteristic All patients (n=73) Median age (range) 64 (36-82) ➢ Heavily pretreated population Number of prior systemic anticancer regimens ➢ Over 65% of patients with 2 or more prior lines of treatment 1 (%) 22 (30%) 2 (%) 32 (44%) ➢ Prior EGFR TKI treatment in ≥3 (%) 16 (22%) 37% of patients Median (range) 2 (0-9) ➢ Over 50% of patients treated Prior EGFR TKI (non-Ex20) 27 (37%) previously with checkpoint Prior pozio and/or mobo (%) 4 (5%) inhibitor Prior checkpoint inhibitor therapy (%) 39 (53%) Brain mets at baseline (%) 28 (38%) 8
Differentiated safety and tolerability profile of CLN-081 at proposed RP2D Dose (BID) 100 mg 150 mg Overall Safety Population (n, %) 39 11 73 100 mg BID nominated as RP2D Grade 1 TRAE of interest Skin Rash 21 (54) 4 (36) 38 (52) At 100 mg BID (N=39): Diarrhea 10 (26) 1 (9) 14 (19) ➢ No Gr ≥3 rash/diarrhea Elevated ALT / AST 2 (5) 1 (9) 6 (8) ➢ Rash/diarrhea 3:1 Gr 1:2 ratio Anemia 3 (8) -- 5 (7) ➢ No systematic GI prophylaxis Grade 2 TRAE of interest ➢ One pt with G3 pneumonitis* Skin Rash 7 (18) 1 (9) 14 (19) Diarrhea 3 (8) 1 (9) 4 (5) At 150 mg BID (N=11): Elevated ALT / AST 2 (5) -- 2 (3) ➢ Expanded enrollment Anemia 1 (3) -- 2 (3) discontinued after 11 patients Grade 3 TRAE of interest ➢ G3: diarrhea (2), rash (1), Skin Rash -- 1 (9) 1 (1) pneumonitis (1)**, Diarrhea -- 2 (18) 2 (3) Transaminitis (1); G4 Elevated ALT / AST 2 (5) 2 (18) 6 (8) Transaminitis (1) Anemia 1 (3) 2 (18) 5 (7) ➢ Increased dose reduction Treatment Related Dose Reduction 5 (13) 3 (27) 10 (14) and/or discontinuation Treatment Related Dose Discontinuation 1 (3) 2 (18) 5 (7) *Patient reported as G3 drug-related pneumonitis (confounded by recent treatment with CPI, concurrent hydropneumothorax in contralateral lung) 9 **Patient reported as G3 drug-related pneumonitis (confounded by concurrent pneumocystis infection, had stopped CLN-081 3 weeks prior to event)
PK profile consistent with clinical safety profile Average Unbound Plasma Concentration over Time 1000 ➢ CLN-081 PK well-behaved to date GI -WT EGFR 50 ➢ Sustained PK exposure over GI50 for ex20ins 100 EGFR for 8h post dose GI -Ex20insASV 50 GI -Ex20insSVD ➢ Limited time of exposure 50 over GI50 for WT EGFR 10 at doses < 100 mg BID ➢ Consistent with clinical safety profile at 100 mg 1 versus 150 mg BID dose 0 1 2 3 4 5 6 7 8 9 Time (h) Data from Phase 1 patients. Uses standard error of the mean. 10 uConc. (ng/mL)
Encouraging response rate in expanded cohort at RP2D 100 mg BID 150 mg BID Overall Response (n=36), RP2D (n=11) (n=70) Best Response, n (%) PR (Confirmed) 14 (39) 3 (27) 25 (36) PR (Pending) 1 (3) -- 1 (1) PR (Unconfirmed) 3 (8) 2 (18) 7 (10) Stable Disease (SD) 17 (47) 5 (45) 34 (49) Progressive Disease (PD) 1 (3) 1 (9) 3 (4) ➢ Stable disease or PR observed in 35/36 (97%) of patients at RP2D 11
Durable objective responses and extended stable disease in patients treated at 100 mg BID 100mg BID Cohort: Duration of Treatment (Months) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 N771delinsGY Pending NGS D770_N771insSVD D770_N771insSVD D770_N771insY Pending NGS D770_N771insSVD D770_N771insG D770_N771insSVD V769_D770InsASV V769_D770InsASV V769_D770InsASV V769_D770insASV D770_N771insSVD V769_D770insASV D770delinsGY Pending NGS H773_V774insNPH➢ Durable objective responses and D770_N771insSVD Pending NGS extended stable disease observed D770_N771insSVD N771_P772insG Pending NGS N771delInsHH ➢ Antitumor activity across spectrum H773delinsTY V769_D770insASV of ex20in mutational sub-types D770_N771insSVD V769_D770InsASV N771delinGD Pending NGS D770_N771insSVD A763_Y764insFQEA V769_D770insASV H773delinsTY D770_N771insSVD V769_D770insASV Partial Response On Partial Response Progressive Stable Disease (Unconfirmed) Treatment (Confirmed) Disease 12 Exon 20 Mutation
Tumor regression observed in majority of patients treated at 100 mg BID 100mg BID Cohort: % Δ from Baseline in Target Lesions 100% ➢ Tumor regression observed in 33/36 (92%) treated patients 80% ➢ Patients respond post EGFR TKI (E) or post checkpoint inhibitor (C) 60% 40% 20% E * 0% E E * C C C -20% E/C E C C C E/C C C -40% C C E/C C C C E C C E -60% -80% E/C -100% C E C Progressive Disease Prior EGFR TKI Prior Checkpoint Inhibitor Partial Response Unconfirmed Partial Response Stable Disease * PD due to progression of non-target lesions. 13 Best Response & % change from baseline (sum of target lesions)
CLN-081 acts rapidly: Tumor regression in 86% of 100mg BID patients at first assessment 100mg BID Cohort: Change from baseline (sum of target lesions) 100% 80% 60% 40% 20% 0% -20% -40% -60% -80% -100% 0 42 105 168 231 294 357 420 483 Days First on-treatment scan 14 % Change from Baseline (Sum of Legions)
Durability profile building for patients treated at RP2D Phase 1 Patients at 100 mg BID (n = 13) *Duration of Response, Median >15 months *Progression Free Survival, Median 12 months **Disease Control Rate 92% * Based upon Kaplan-Meier estimates ** Disease control rate (DCR): % of patients with stable disease ≥6 months or any PR ➢ Follow-up on Phase 1 patients at 100 mg BID shows encouraging response duration, progression-free survival and disease control rates. ➢ Follow-up ongoing in Phase 2a patients at 100 mg BID. 15
Disease control rates in patients treated at 100 mg BID based on baseline CNS status Phase 1 Patients at 100 mg BID* Disease Control Rate (DCR)**, All (N=13) 92% ➢ CNS Disease History at Baseline (N=4) 100% ➢ No CNS Disease History at Baseline (N=9) 89% * Patients with stable, treated brain metastases included; active, untreated brain metastases excluded ** Disease control rate (DCR): % of patients with stable disease ≥6 months or any PR ➢ Disease control rates comparable, irrespective of CNS disease status at baseline in patients treated at 100 mg BID ➢ Examples of patients with reductions in CNS lesions have been noted 16
CLN-081 Conclusions and next steps • Updated data at the proposed RP2D of 100 mg BID, reaffirms differentiated clinical profile for CLN-081 (an oral TKI) Summary • High response rate maintained with expanded patient numbers at RP2D • Durable responses and encouraging PFS • Antitumor activity across a spectrum of EGFR ex20ins mutational sub-types, and Efficacy in patients who progress on other EGFR ex20ins TKI • Differentiated safety and tolerability profile with reduced rate of all-grade diarrhea, and no grade 3 diarrhea or rash to date at RP2D Safety • Reduced rates of dose reduction/discontinuation • Move rapidly toward a potentially pivotal 2L trial, and expand clinical development to the 1L setting Next Steps • Regulatory update planned in Q1 2022 17
Nadim Ahmed Jon Wigginton, MD Chief Executive Officer Senior Advisor & Chairman of SAB Q&A Leigh Zawel, PhD Jeff Trigilio Chief Scientific Officer, Small Molecules Chief Financial Officer