tptx-8k_20210405.htm
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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): April 5, 2021

TURNING POINT THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

 

 

 

 

 

Delaware

 

001-38871

 

46-3826166

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

 

 

 

10628 Science Center Drive, Suite 200, San Diego, CA

 

92121

(Address of Principal Executive Offices)

 

(Zip Code)

Registrant’s Telephone Number, Including Area Code: (858) 926-5251

N/A

(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 (see General Instruction A.2. below):

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, $0.0001 par value
per share

 

TPTX

 

The Nasdaq Stock Market LLC

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.


 

 

 


 

 

Item 8.01.  Other Events.

On April 5, 2021, Turning Point Therapeutics, Inc. (the “Company”) reported initial data from the Company’s Phase 1/2 SWORD-1 clinical study of the Company’s RET inhibitor drug candidate TPX-0046.

Twenty-one patients enrolled in the study including 10 with non-small cell lung cancer (“NSCLC”) and 11 with medullary thyroid carcinoma (“MTC”) who were treated from December 2019 to the data cut-off date of March 10, 2021. Patients included those with RET-altered tyrosine kinase inhibitor (“TKI”)-naïve NSCLC (n=3; all previously treated with platinum-based chemotherapy and immunotherapy) and MTC (n=2), and TKI-pretreated NSCLC (n=7) and MTC (n=9).

All 16 TKI-pretreated patients were previously treated with a selective RET TKI and 9 patients (56%) were treated with more than 1 prior TKI. Ninety one percent of patients (19/21) had a baseline Eastern Cooperative Oncology Group (ECOG) performance score of 1, and nearly half (10/21) received 3 or more prior therapies.

Preliminary efficacy data by investigator assessment was available for 14 evaluable patients with baseline measurable disease and at least one post-baseline assessment per RECIST v1.1, including TKI-naïve NSCLC (n=3) and MTC (n=2), and TKI-pretreated NSCLC (n=4) and MTC (n=5).

As of the March 10, 2021 data cut-off date:

Preliminary Safety and Pharmacokinetic Results

 

A total of 21 patients with RET-altered NSCLC or MTC were treated with TPX-0046 across multiple doses and schedules from 10mg once daily (“QD”) to 30mg QD.

 

TPX-0046 was generally well tolerated, with the most frequent treatment emergent adverse event (“TEAE”) being Grade 1 or 2 dizziness.

 

The maximum tolerated dose had not been determined, with 1 dose-limiting toxicity of treatment-related Grade 2 gait disturbance at 30 mg QD.

 

TEAEs reported in greater than 20 percent of patients were dizziness (43%); fatigue (38%); alkaline phosphatase increase, constipation, decreased appetite, dry mouth, hyperphosphataemia, lipase increase (29% each); and alanine aminotransferase increase, dehydration, and muscular weakness (24% each).

 

There were infrequent dose reductions or drug discontinuations due to TEAEs.

 

The majority of treatment related adverse events (“TRAEs”) were Grade 1 or 2 and there were no Grade 4 or 5 TRAEs

 

There were no treatment related Grade 3 or greater ALT/AST elevations, any grade of hypertension, hemorrhagic events or QT prolongation, and no interstitial lung disease or pneumonitis.

 

Preliminary pharmacokinetic data indicates exposure increases in a dose dependent manner.

Preliminary Efficacy Results

 

Of 5 RET TKI-naïve patients, 4 showed tumor regressions of -42%, -37%, -23%, and -3%, including 2 patients dosed at 30 mg QD who achieved confirmed partial responses with duration of responses of 5.6 and 5.8+ months respectively.  Three of the 4 patients with regressions remained on treatment awaiting their next scan.

 

Of 9 TKI-pretreated patients, 3 patients (2 treated with only 1 prior selective RET TKI) achieved tumor regressions of -44%, -27% and -17%. All 3 patients remained on treatment awaiting their next scan.

 

 

 


 

Of the 14 evaluable patients, 7 (50%) remained on treatment with duration of treatment ranging from 5.1 to 51+ weeks.

The Company continues to evaluate doses and schedules to determine a recommended Phase 2 dose. After determination of the recommended Phase 2 dose, the Company plans to study TPX-0046 in multiple Phase 1 dose expansion cohorts in up to 75 patients with RET-altered malignancies, prior to an end of Phase 1 meeting with the Food and Drug Administration.

In connection with the report of the above initial data, the Company referred to the presentation attached hereto as Exhibit 10.1, which is incorporated herein by reference.

Forward-Looking Statements

Certain statements contained in this report are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include, without limitation, statements regarding, among other things, the efficacy, safety and therapeutic potential of TPX-0046, the results, conduct, progress and timing of the Phase 1/2 clinical study of TPX-0046, plans regarding future clinical studies and regulatory discussions, and the regulatory approval path for TPX-0046. Words such as “will”, “expect”, “may,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. For such statements, we claim the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from our expectations. Factors that could cause actual results to differ materially from the forward-looking statements include, but are not limited to, risks and uncertainties associated with market conditions, the satisfaction of customary closing conditions related to the public offering and the COVID-19 global pandemic. Additional factors that could cause actual results to differ materially from those stated or implied by our forward-looking statements are disclosed in our filings with the SEC. These forward-looking statements represent our judgment as of the time of this report. We disclaim any intent or obligation to update these forward-looking statements, other than as may be required under applicable law.

 

Item 9.01

Financial Statements and Exhibits.

(d) Exhibits.

 

 

 

 

Exhibit
No.

  

Description

 

 

10.1

  

April 5, 2021 Turning Point Therapeutics, Inc. Presentation.

 

 

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.

 

 

 

 

 

 

 

 

 

 

 

 

TURNING POINT THERAPEUTICS, INC.

 

 

 

 

Date: April 5, 2021

 

 

 

By:

 

/s/ Annette North

 

 

 

 

 

 

Annette North

 

 

 

 

 

 

Executive Vice President and General Counsel

 

 

 

 

 

Slide 1

April 5, 2021 Initial Preliminary Data from Ongoing SWORD-1 Phase 1/2 Study of TPX-0046 Exhibit 10.1

Slide 2

Forward-Looking Statements Statements in this Presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our research and clinical development activities, plans and projected timelines, business strategy and plans, regulatory matters, objectives of management for future operations, market size and opportunity, our ability to complete certain milestones and our expectations regarding the relative benefits of our drug candidates versus competitive therapies. Words such as “believe,” “can”, “continue,” “anticipate,” “could,” “estimate,” “plan,” “predict,” “expect,” “intend,” “will,” “may,” “goal,” “upcoming,” “near term”, “milestone”, “potential,” “target” or the negative of these terms or similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include, without limitation: our preclinical studies and clinical trials may not be successful; regulatory authorities, including the U.S. Food and Drug Administration (FDA) may not agree with our interpretation of the data from clinical trials of our drug candidates; we may decide, or regulatory authorities may require us, to conduct additional clinical trials or to modify our ongoing clinical trials; we may experience delays in the commencement, enrollment, completion or analysis of clinical testing for our drug candidates, or significant issues regarding the adequacy of our clinical trial designs or the execution of our clinical trials may arise, which could result in increased costs and delays, or limit our ability to obtain regulatory approval; our drug candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or inadequate therapeutic efficacy of our drug candidates could delay or prevent regulatory approval or commercialization; the COVID-19 pandemic may disrupt our business and that of third parties on which we depend, including delaying or otherwise disrupting our research and development activities; and we may not be able to obtain additional financing. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this Presentation is given. Other risks and uncertainties affecting us are described more fully in our filings with the Securities and Exchange Commission. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. This Presentation discusses a drug candidate that is under clinical study and which has 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 this drug candidate for the use for which such drug candidate is being studied. 2

Slide 3

3 Compact macrocycle with a small binding interface Potently inhibits wildtype RET and multiple RET mutations in cellular assays, demonstrates tumor regression in xenograft models VEGF sparing, potential to provide improved safety over approved agents Potential opportunity in TKI-naïve and TKI-pretreated patients following selective RET TKIs Retevmo and Gavreto, where there is no approved targeted therapy TPX-0046 is a Potent Next Generation RET Tyrosine Kinase Inhibitor

Slide 4

4 Current SWORD-1 Phase 1/2 Study Design of TPX-0046 in Patients with Advanced Solid Tumors Harboring RET Fusion or Mutation Population Adults with advanced solid tumors RET fusion or mutation assessed by local testing No limit on # of prior therapies Prior RET TKI allowed ECOG Performance Status 0 or 1 Asymptomatic CNS disease allowed Design 3+3 with expansion allowed at doses where clinical activity is observed Response evaluation by RECIST v1.1 10 mg QD N=3 20 mg QD N=4 Doses evaluated from 16 Dec 2019 to 10 Mar 2021 Dose evaluation ongoing Phase 1 Dose Escalation (n=21) 10 mg BID N=4 30 mg QD N=5 20 mg  30mg QD N=3 20 mg BID N=2 Primary Objectives: Evaluate safety/tolerability and determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) Phase 2 (n~300) RP2D RET Fusion+ NSCLC RET TKI-Naïve RET Fusion+ NSCLC 1 Prior RET TKI Treated RET Mutation+ Medullary Thyroid Carcinoma RET TKI-Naïve RET Mutation+ Medullary Thyroid Carcinoma 1 Prior RET TKI Treated RET Fusion or Mutation+ Other Solid Tumors RET TKI-Naïve RET Fusion or Mutation+ Other Solid Tumors RET TKI-Pretreated

Slide 5

5 Enrolled Subjects N=21 10 NSCLC, 11 MTC Evaluable Subjectsa N=14b TKI-Naïve (N=5) 3 NSCLC 2 MTC TKI-Pretreated (N=9) 4 NSCLC 5 MTC NSCLC: non-small cell lung cancer; MTC: medullary thyroid carcinoma; TKI: tyrosine kinase inhibitor Data Cutoff Date: March 10, 2021 a Patients with baseline measurable disease, received at least one dose of study drug, and at least one post-baseline assessment per RECIST v1.1 b As of data cut-off date, 5 patients off treatment and 2 patients on treatment awaiting first post-baseline assessment Subject Disposition

Slide 6

Demographics and Baseline Characteristics 6 * Selective TKI includes selpercatinib or pralsetinib TKI: tyrosine kinase inhibitor; NSCLC: non-small cell lung cancer; MTC: medullary thyroid carcinoma. Data Cutoff Date: March 10, 2021

Slide 7

TPX-0046 Preliminary Safety Summary TPX-0046 has been generally well tolerated Most AEs were Grade 1 or 2 Most common TEAE was dizziness Infrequent dose modifications due to TEAE 4 (19%) patients with TEAEs that led to dose reduction 2 (10%) patients with TEAEs that led to drug discontinuation MTD not reached; 1 DLT at 30 mg QD* No treatment related Grade≥3 ALT/AST elevation No treatment related hypertension, hemorrhagic events, QT prolongation, or ILD/pneumonitis of any Grade Median duration of treatment: 7.9 weeks (range 1.6 – 51.0+ weeks) 7 TEAE: treatment emergent adverse event; TRAE: treatment related adverse event; MTD: maximum tolerated dose; DLT: dose-limiting toxicity. Data Cutoff Date: March 10, 2021 * DLT was reported as treatment related Grade 2 gait disturbance.

Slide 8

TPX-0046 Preliminary Efficacy by Investigator Assessment 8 Of 5 RET TKI-naïve patients: 2 with confirmed PRs at 30 mg QD (DORs: 5.6 and 5.8+ months) Of 9 RET TKI-pretreated patients: 2 have stable disease with tumor reductions of -27% and -17% Both patients remained on treatment awaiting next scan TKI: tyrosine kinase inhibitor; NSCLC: non-small cell lung cancer; MTC: medullary thyroid carcinoma; DOR: duration of response. Data Cutoff Date: March 10, 2021 # Patients remained on treatment

Slide 9

TPX-0046 Preliminary Efficacy by Investigator Assessment TKI-Pretreated Patients 9 Of 9 RET TKI-pretreated patients: 4 received 1 prior selective TKI 3 received 3 or more prior TKIs 2 received 2 prior TKIs TKI: tyrosine kinase inhibitor; NSCLC: non-small cell lung cancer; MTC: medullary thyroid carcinoma; DOR: duration of response. Data Cutoff Date: March 10, 2021 # Patients remained on treatment Treated with 1 prior selective RET TKI

Slide 10

TPX-0046 Duration of Treatment 10 PR: partial response; PD: progressive disease; NSCLC: non-small cell lung cancer; MTC: medullary thyroid carcinoma. Data Cutoff Date: March 10, 2021 Duration of Treatment TKI-Naïve (n=5): 8.9 to 51.0+ weeks TKI-Pretreated (n=9): 5.1 to 41.3+ weeks

Slide 11

Case 1: TKI-Naïve MTC Patient Demographics 62 years old male with sporadic metastatic MTC Post-thyroidectomy follow up evaluation showed rising tumor markers (doubling calcitonin and CEA over 2 months) and MRI revealed liver metastases Molecular Characteristics RET D631-L633delInsE Prior Treatment History None TPX-0046 Treatment Course Received TPX-0046 at 30 mg QD Best response: confirmed PR (-42% SLD); patient remained on treatment in Cycle 11 at time of data cutoff Baseline Cycle 11 11 Tumor Markers MTC: medullary thyroid carcinoma; CEA: carcinoembryonic antigen; QD: once daily; SLD: sum of longest diameter

Slide 12

Demographics 54-year old male with metastatic NSCLC Molecular Characteristics KIF5B-RET by NGS Prior Treatment History 1) Selpercatinib for 9 months 2) Carboplatin/ Pemetrexed/ Pembrolizumab TPX-0046 Treatment Course Received TPX-0046 at 30 mg QD Best response: SD (−27% SLD); patient remained on treatment in Cycle 11 at time of data cutoff Case 2: TKI-Pretreated NSCLC Patient NSCLC: non-small cell lung cancer; NGS: next-generation sequencing; QD: once daily; SD: stable disease; SLD: sum of longest diameter 12 Baseline Cycle 11

Slide 13

TPX-0046 Phase 1 Early Data Key Takeaways TPX-0046 has an encouraging emerging profile and dose evaluations are ongoing Majority of patients were heavily pretreated with nearly half of patients having received >3 prior therapies TPX-0046 was generally well tolerated. MTD was not reached with 1 DLT at 30 mg QD Among 14 efficacy evaluable patients, preliminary data show clinical activity TKI-Naïve: confirmed PRs (NSCLC and MTC) TKI-Pretreated: SDs with tumor reductions (-27% and -17%; both remained on treatment awaiting next scan) Protocol amendment planned to evaluate TPX-0046 in Phase 1 expansion cohorts 13 Data Cutoff Date: March 10, 2021

Slide 14

Next Steps Evaluating multiple doses and schedules to determine RP2D Modifying Phase 1 protocol to evaluate TPX-0046 in expansion cohorts in up to 75 patients: 14 Currently evaluating 30 mg QD, 2040 mg QD, and 20 mg BID dose levels* RP2D Phase 1 Dose Finding * Additional doses and/or schedules may be explored. RP2D: recommended phase 2 dose

Slide 15

April 5, 2021 Initial Preliminary Data from Ongoing SWORD-1 Phase 1/2 Study of TPX-0046

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