8-K
false000159589300015958932021-10-082021-10-08

 

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): October 08, 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, Ste. 200

 

San Diego, California

 

92121

(Address of Principal Executive Offices)

 

(Zip Code)

 

hRegistrant’s Telephone Number, Including Area Code: 858 926-5251

 

 

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

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


Title of each class

 

Trading
Symbol(s)

 


Name of each exchange on which registered

Common Stock, $0.0001 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 October 8, 2021, Turning Point Therapeutics, Inc. (the “Company”) updated its corporate slide presentation (the “Updated Presentation”) for use in meetings with investors, analysts and others. The Updated Presentation is available through the Company’s website and a copy of the Updated Presentation is attached hereto as Exhibit 99.1 and incorporated herein by reference.

 

On October 8, 2021, the Company issued a press release announcing early clinical data from the NTRK-positive tyrosine kinase inhibitor (“TKI”)-naïve and TKI-pretreated advanced solid tumor cohorts (EXP-5 and EXP-6) of the ongoing TRIDENT-1 Phase 1/2 study of its lead drug candidate, repotrectinib.

 

Repotrectinib Early Data from Phase 1/2 TRIDENT-1 Study from NTRK-Positive Advanced Solid Tumor Cohorts (EXP-5, EXP-6)

 

The early Phase 2 TRIDENT-1 dataset utilizes an August 26, 2021 data cutoff. The safety analysis includes 301 treated patients from the pooled Phase 1 and Phase 2 portions of TRIDENT-1 across all cohorts, and the preliminary efficacy analysis includes 40 evaluable patients from the pooled Phase 1 and Phase 2 portions of TRIDENT-1 in the NTRK-positive advanced solid tumor cohorts (EXP-5, EXP-6). Of the 40 patients, 17 were TKI-naïve and 23 were TKI-pretreated. Phase 2 patients included in the efficacy analysis had baseline measurable disease and at least one post-baseline evaluable scan or were off treatment prior to first post-baseline scan. Responses were confirmed with a subsequent scan at least 28 days later per RECIST 1.1 and were determined by physician assessment for Phase 2 patients. Phase 1 patients included in the efficacy analysis were treated at or above the Phase 2 dose, with responses assessed by blinded independent central review. The Phase 1 data cutoff date was July 22, 2019 for responses and August 26, 2021 for duration of treatment.

 

Pooled Phase 1 and Phase 2 Preliminary Efficacy Analysis (n=40)

In the NTRK-positive TKI-naïve advanced solid tumor population (EXP-5: n=17), the confirmed Objective Response Rate (“cORR”) was 41% (95% CI: 18-67). At the time of the data cutoff, three patients with limited time on treatment achieved stable disease with tumor regression of -21%, -23%, and -27% on their first post-baseline scans, and were awaiting their next scans. Duration of response ranged from 1.9+ to 7.4+ months, and the duration of treatment in the 17 patients ranged from 0.9 to 30.7+ months.
In the NTRK-positive TKI-pretreated advanced solid tumor population (EXP-6: n=23), the cORR was 48% (95% CI: 27-69). As of the cutoff date, three patients had unconfirmed partial responses (“uPRs”). Two uPRs has been confirmed since the cutoff date and are included in the cORR of 48%; the third patient with a uPR was on treatment awaiting a confirmatory scan and is not considered a responder in the cORR. Duration of response ranged from 0.9+ to 15.1 months, and the duration of treatment in the 23 patients ranged from 0.6 to 20.8 months.
Of the 23 NTRK-positive TKI-pretreated advanced solid tumor patients, 13 (57%) had NTRK solvent front mutations. In these 13 patients, the cORR was 62% (95% CI: 32-86) including one patient who had a complete response. As of the cutoff date, three patients had uPRs. Two uPRs have been confirmed since the cutoff date and are included in the cORR; the third patient with a uPR was on treatment awaiting a confirmatory scan and is not considered a responder in the cORR. Duration of response ranged from 0.9+ to 13.7 months.

 

Preliminary Safety Analysis (n=301)

Repotrectinib was generally well tolerated.
The most frequently reported treatment-emergent adverse event (“TEAE”) was low-grade dizziness (60%) of which 76% of reported cases were grade 1. 11 patients (4%) reported ataxia in the absence of dizziness. No events of dizziness or ataxia led to treatment discontinuation.
Dose modifications due to TEAEs included 27% of patients who had dose reduction and 11% who had drug discontinuation.

 

The Company also announced the publication of preclinical data of repotrectinib in the American Association of Cancer Research’s peer reviewed journal, Molecular Cancer Therapeutics. Preclinical studies described in the publication titled “Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations” show that repotrectinib potently inhibited TRK fusion proteins and resistance mutations. Repotrectinib was the most potent inhibitor of wild-type TRKA/B/C fusions and was more potent than selitrectinib against all tested resistance mutations.

 

Repotrectinib was recently granted Breakthrough Therapy designation for the treatment of patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK tyrosine kinase inhibitors, with or without prior chemotherapy, and have no satisfactory alternative treatments. The Company is planning to discuss next steps towards potential registration of repotrectinib in this patient population at a Type B meeting with the U.S. Food and Drug Administration anticipated in the first half of 2022.


 

Forward-Looking Statements
 

Statements contained in this report regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of repotrectinib, the results, conduct, progress and timing of the TRIDENT-1 clinical study, plans regarding future regulatory submissions, and the regulatory approval path for repotrectinib. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans”, “will”, “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with the Company’s business in general, risks and uncertainties related to the impact of the COVID-19 pandemic to the Company’s business and the other risks described in the Company’s filings with the Securities and Exchange Commission (“SEC”), including its quarterly report on Form 10-Q filed with the SEC on August 9, 2021. All forward-looking statements contained in this report speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

Exhibit

 

 

No.

 

Description

 

 

99.1

 

Presentation Materials of Turning Point Therapeutics, Inc.

 

 

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 thereunto duly authorized.

 

 

 

TURNING POINT THERAPEUTICS, INC.

 

 

 

 

Date:

October 8, 2021

By:

/s/ Annette North

 

 

 

Annette North
Executive Vice President and General Counsel

 


Slide 1

October 2021 Next-Generation Precision Oncology Medicines Company Overview Exhibit 99.1


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 drug candidates that are under 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 drug candidates for the use for which such drug candidates are being studied.


Slide 3

Lead Candidate: Repotrectinib with 2 Breakthrough Therapy Designations¹ NSCLC Other Solid Tumors Robust Pipeline with Four Clinical Stage Drug Candidates Developing potential best-in-class drug candidates Inhibitor of JAK2, SRC and FAK Combination potential with KRAS-targeting agents, with first cohort planned in KRAS mutant G12D solid tumors Inhibitor of ROS1 and TRK² Best-in-class potential in TKI-naïve and TKI-pretreated ROS1+ NSCLC, and TKI-pretreated TRK+ solid tumors Early Stage Pipeline Elzovantinib (TPX-0022) Inhibitor of MET, CSF1R and SRC Encouraging early clinical activity, supporting development as monotherapy and in combinations TPX-0046 Inhibitor of RET Encouraging early clinical activity, supporting development in TKI-naïve and TKI-pretreated settings TPX-0131 Inhibitor of ALK Highly potent and CNS penetrant in preclinical studies Leveraging strategies for rapid proof-of-concept data and accelerated paths to market Development and commercial synergies across the portfolio $1.1 billion in cash, cash equivalents and marketable securities, as of 30-Jun-2021, expected to fund current operations into 2024 ¹ Breakthrough Therapy designation granted in (1) ROS1+ metastatic NSCLC patients who have not been treated with a ROS1 TKI; and (2) patients with adv. solid tumors that have an NTRK gene fusion who have progressed following treatment with 1 or 2 prior TRK TKIs, with or without prior chemotherapy, and have no satisfactory alternative treatments. ² Also being studied in pediatric patients harboring ALK, ROS1 or NTRK1-3 alterations. Pancreatic NSCLC CRC Endometrial Other Solid Tumors NSCLC NSCLC Gastric Other Solid Tumors NSCLC Thyroid Other Solid Tumors Deep expertise in tumor biology and structure-based drug design


Slide 4

Discovery Preclinical Early Stage Clinical Development Late Stage Clinical Development Repotrectinib (ROS1/TRK) TRIDENT-1: Advanced NSCLC (ROS1) and solid tumors (NTRK) CARE: Pediatric advanced solid tumors TRIDENT-2: KRAS-targeting combination Elzovantinib (TPX-0022) (MET) SHIELD-1: Advanced solid tumors SHIELD-2: EGFR combination TPX-0046 (RET) Advanced solid tumors TPX-0131 (ALK) Advanced NSCLC Discovery Programs KRAS G12D p21 Activated Kinase Multiple GTPase Oncology Targets Ongoing Clinical Studies Against Well Validated Oncogenic Targets Note: Turning Point retains worldwide rights for all pipeline assets, except for repotrectinib and elzovantinib (TPX-0022) in Greater China (partnered with Zai Lab).


Slide 5

Single Agent 4,5 6 4,7-8 9-12 4,5 13-15 4,16 Combos 4,17-19 20-24 25-29 Single Agent and Combination Opportunities To Treat Patients with Biomarker Driven Cancers ¹ American Cancer Society 2020. ² Bailey MH, et al: Cell 2018. ³ Estimates rounded and include locally advanced and metastatic populations per SEER, based on incidence reported by American Cancer Society Cancer Facts & Figures 2020 (US) and GLOBOCAN 2018 (EU5). 4 Zappa, et al: Transl Lung Cancer Res 2016. 5 Hirsch FR, et al: Lancet 2017. 6 Rosen EY, et al: Clin Cancer Res 2020. 7 Drilon A, et al: J Thorac Oncol. 2017. 8 Overbeck TR, et al: Translational lung cancer research 2020; based on gene copy number of 10 or greater. 9 Loberg RD et al: Journal of Clinical Oncology 2014. 10 Yang Y, et al: Gastric Cancer 2016. 11 Inokuchi M, et al: World J Gastrointest Oncol. 2015. 12 Lennerz JK, et al: J Clin Oncol. 2011. 13 Includes MTC and PTC. For MTC, based on weighted average of sporadic (75%) and familial (25%) per American Cancer Society, with biomarker frequencies of 60% (Taccaliti A, et al: Curr Genomics 2011) and 98% (Elisei R, et al: Genes (Basel) 2019), respectively. 14 Lee MY, et al: Cancer Res Treat. 2017. 15 Prescott JD, et al: Cancer 2015. 16 Garber K.: J Natl Cancer Inst. 2010. 17 Assumes 15% of US and EU5 NSCLC patients are EGFR+ (Hirsch FR, et al: Lancet 2017). Does not account for proportion of patients who will not progress to a 2L therapy. 18 Ramalingam SS, et al: Annals of Oncology 2018. 19 Bean J, et al: Proc Natl Acad Sci U S A 2007. 20 Includes NSCLC, CRC, pancreatic cancer and endometrial cancer. 21 Liu S, et al: JCO. 2020. 22 Neumann J et al: Pathology – Research and Practice. 2009. 23 Bournet B, et al: Clin Transl Gastroenterol. 2016. 24 Krakstad C, et al: PLoS One. 2012. 25 Based on repotrectinib combination data presented at AACR 2020 showing synergy in certain mutant KRAS models. 26 Includes NSCLC, CRC and pancreatic cancer. 27 Biernacka A, et al: Cancer Genet 2016. 28 Nassar A et al: NEJM. 2021. 29 Thein K et al: JCO. 2020. estimated patients diagnosed with solid tumors annually in the US and EU5¹ of tumors harbor potentially actionable targets² 3.4 MILLION 57%


Slide 6

Repotrectinib: A Highly Selective ROS1/TRK Inhibitor


Slide 7

ATP Kinase Repotrectinib Solvent-Front mutation Gatekeeper mutation Highly potent, structurally differentiated: small (low molecular weight), compact, with a rigid 3D macrocycle Designed to bind completely inside the ATP pocket even in the presence of solvent front or gatekeeper mutations Potential to address resistance from prior lines of TKI therapy May also prevent or delay the emergence of new resistant mutations Repotrectinib: Potential Best-in-Class ROS1 and NTRK Targeted Therapy in TKI-Naïve and Treatment Resistance Settings


Slide 8

TRIDENT-1: An Ongoing Phase 1/2 Study of Repotrectinib in Patients with Advanced Solid Tumors Harboring ROS1, NTRK1-3 Rearrangements


Slide 9

TRIDENT-1 Study Design and Preliminary Phase 1+2 Data ROS1+ Advanced NSCLC NTRK+ Advanced Solid Tumors EXP-1 ROS1 TKI naïve (n=55) EXP-2 1 prior ROS1 TKI AND 1 platinum-based chemotherapy (n=60) EXP-3 2 prior ROS1 TKIs AND No prior chemotherapy (n=40) EXP-4 1 prior ROS1 TKI AND No prior chemotherapy (n=60) EXP-5 TRK TKI naïve (n=55) EXP-6 TRK TKI pretreated (n=40) cORR 39% (n=23) (95% CI: 20-61) cORR 30% (n=10) (95% CI: 7-65) cORR 38% (n=39) (95% CI: 23-55) cORR 91% (n=22) (95% CI: 71-99) cORR 41% (n=17) (95% CI: 18-67) cORR 48% (n=23) (95% CI: 27-69) Phase 2 Primary Objective cORR by BICR in each expansion cohort Phase 2 Secondary Objectives DOR, PFS, and OS IC-ORR and CNS-PFS Note: EXP-1 data presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer. Phase 2 data cutoff date of 31-Dec-2020 with responses confirmed by physician assessment. Data pooled from the Phase 1 portion (treated at or above the Phase 2 dose) with patients from the Phase 2 portion who had at least two post-baseline scans. EXP-2, EXP-3, EXP-4, EXP-5 and EXP-6 data presented at the 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics. Phase 2 data cutoff date of 26-Aug-2021 with responses confirmed by physician assessment. Data pooled from the Phase 1 portion (treated at or above the Phase 2 dose) with patients from the Phase 2 portion who had at least one post-baseline evaluable scan or were off treatment prior to first post-baseline scan. EXP-4 and EXP-6 data updated since pre-recorded presentations at the AACR-NCI-EORTC conference. Phase 1 data cutoff of 22-Jul-2019 with responses confirmed by Blinded Independent Central Review (BICR). Responses confirmed per RECIST v1.1. CI: confidence interval; EXP: expansion; NSCLC: non-small cell lung cancer; cORR: confirmed objective response rate; TKI: tyrosine kinase inhibitor; SFM: solvent front mutation SFM G2032R cORR 53% (n=15) (95% CI: 27-79) SFMs cORR 62% (n=13) (95% CI: 32-86)


Slide 10

ROS1+ TKI-Naïve Advanced NSCLC: Preliminary Clinical Activity Overall Response (N=22) N=22 patients with baseline and at least two post baseline scans N=15 Phase 2 patients N=7 Phase 1 patients treated at or above the Phase 2 recommended dose As of 31 December 2020, the 16th patient in Phase 2 has an unconfirmed PR and is on treatment awaiting a second post-baseline confirmatory scan. Phase 2 N=15 Phase 1+2 N=22 Confirmed ORR (95% CI) 93% (68 – 100) 91% (71 – 99) Duration of Response 1.25+ – 7.4+ months (range) 1.25+ – 17.6+ months (range) Presented at World Lung 2020 in Jan-2021 Note: Presented at World Lung 2020 in Jan-2021. Phase 2 data cutoff of 31-Dec-2020, responses confirmed by Physician Assessment. Phase 1 data cutoff of 22-Jul-2019, responses confirmed by Blinded Independent Central Review (BICR). Phase 1 data includes only patients treated at or above the Phase 2 recommended dose of repotrectinib. cORR: confirmed objective response rate; ORR: objective response rate


Slide 11

ROS1+ TKI Naïve Advanced NSCLC: Duration of Treatment Note: Presented at World Lung 2020 in Jan-2021. Data cutoff of 31-Dec-2020. † Includes patients with a baseline and at least two post-baseline scans; Phase 1 data includes only patients treated at or above repotrectinib RP2D. PD: progressive disease; PR: partial response; RP2D: recommended Phase 2 dose Duration of Treatment (N=22):† Phase 1 n=7 Phase 2 n=15 Remaining on treatment, n (%) 2 (29) 14 (93) On treatment >30 months, n (%) 4 (57) – Median Time on treatment, months (range) 30.9 (10.9–37.3) 5.3 (3.7+–10.9+)


Slide 12

ROS1+ TKI-Pretreated Advanced NSCLC: Preliminary Clinical Activity Overall Response (Phase 1 + Phase 2) N=72 EXP-2 EXP-3 EXP-4 Phase 2 (N=16) Phase 1 + 2 (N=23) Phase 2 (N=9) Phase 1 + 2 (N=10) Phase 2 (N=36) Phase 1 + 2 (N=39) Confirmed ORR (cORR) (95% CI) 31% (11 – 59) 39% (20 – 61) 33% (7 – 70) 30% (7 – 65) 36%* (21 – 54) 38%* (23 – 55) Duration of Response (range in months) 1.8+ – 9.2 n=5 1.8+ – 11.1 n=9 1.9+ – 12.9+ n=3 1.9+ – 12.9+ n=3 1.7+ – 15.0+ n=13 0.8+ – 15.0+ n=15 Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. * At time of the 26-Aug-2021 data cutoff, 3 patients in Ph 2 EXP-4 had unconfirmed PR (uPR). All 3 uPRs have been confirmed since the 26-Aug-2021 data cutoff and are included in the cORR. Ph 2: RECIST v1.1 assessed by Physician Assessment with a data cutoff date of 26-Aug-2021. Ph 1: RECIST v1.1  assessed by Blinded Independent Central Review (BICR) with data cutoff date of 22-Jul-2019 for patients with baseline measurable disease and ≥ 1 post-baseline scan. Ph 1 patients  treated at or above the Ph 2 recommended dose. EXP-4 data updated since pre-recorded presentation at the AACR-NCI-EORTC conference.


Slide 13

ROS1+ TKI-Pretreated Advanced NSCLC with Baseline ROS1 Resistance Mutations: Preliminary Clinical Activity Overall Response (Phase 1 + Phase 2) N=18 # Patient with solvent front mutation * Patient with gatekeeper mutation + Patient with other kinase domain mutation Maximum % Change from Baseline in Tumor Size Any ROS1 Resistance Mutation Solvent Front Mutation (G2032R) Phase 2 (N=15) Phase 1 + 2 (N=18) Phase 2 (N=12) Phase 1 + 2 (N=15) Confirmed ORR (cORR) (95% CI) CR PR 47% (21 – 73) 2 (13%) 5 (33%) 50% (26 – 74) 2 (11%) 7 (39%) 50% (21 – 79) 2 (17%) 4 (33%) 53% (27 – 79) 2 (13%) 6 (40%) Duration of Response (range in months) 1.9+ - 15.0+ n=7 1.9+ - 15.0+ n=9 1.9+ - 15.0+ n=6 1.9+ - 15.0+ n=8 Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. 15 of 18 resistance mutations were G2032R solvent front mutations; the other 3 included 1 gatekeeper (L2026M) and 2 other kinase domain mutations (F2004I and L2086F). 2 patients with CR had lymph node response and therefore not at -100% change from baseline. Data cutoff date 26-Aug-2021 for Phase 2 and 22-Jul-2019 for Phase 1.


Slide 14

ROS1+ TKI-Pretreated Advanced NSCLC: Duration of Treatment Duration of Treatment (Phase 1 + Phase 2) N=72 EXP-2 EXP-3 EXP-4 Phase 1 + 2 (N=23) Phase 1 + 2 (N=10) Phase 1 + 2 (N=39) Duration of Treatment (range in months) 0.7 – 44.5+ 0.5 – 18.1+ 0.5 – 19.2+ Patients remaining on treatment – n (%) 5 (22%) 2 (20%) 21 (54%) Patients with confirmed response Phase 1 + 2 (n=9) Phase 1 + 2 (n=3) Phase 1 + 2 (n=15) Duration of Treatment (range in months) 4.5 – 44.5+ 4.8 – 18.1+ 2.9 – 19.2+ Patients with confirmed response remaining on treatment – n (%) 3 (33%) 2 (67%) 10 (67%) Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Phase 2 data cutoff date 26-Aug-2021 (responses confirmed by Physician Assessment). Phase 1 data cutoff date 22-Jul-2019 for responses confirmed by BICR and 26-Aug-2021 for duration of treatment. EXP-4 data updated since pre-recorded presentation at the AACR-NCI-EORTC conference.


Slide 15

NTRK+ TKI-Naive Advanced Solid Tumors: Preliminary Clinical Activity Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Data cutoff date 26-Aug-2021 for Phase 2 and 22-Jul-2019 for Phase 1. Phase 2: RECIST v1.1 assessed by Physician Assessment with a data cutoff date of 26-Aug-2021. Phase 1: RECIST v1.1  assessed by Blinded Independent Central Review (BICR) with data cutoff date of 22-Jul-2019 for patients with baseline measurable disease and ≥ 1 post-baseline scan. Ph 1 patients treated at or above the Ph 2 recommended dose. Overall Response (Phase 1 + Phase 2) N= 17 # Patient remains on treatment. 2 patients not displayed due to discontinuing treatment prior to first post-baseline scan EXP-5 Phase 2 (N=15) Phase 1 + 2 (N=17) Confirmed ORR (cORR) (95% CI) 40% (16 – 68) 41% (18 – 67) Duration of Response (range in months) 1.9+ – 7.4+ n=6 1.9+ – 7.4+ n=7


Slide 16

NTRK+ TKI-Naive Advanced Solid Tumors: Duration of Treatment Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Patient on treatment for 30.7+ months has not had BICR assessment of scans since 22-Jul-2019; per physician assessment, patient was in response for 7.4 months. Phase 2 data cutoff date 26-Aug-2021 (responses confirmed by Physician Assessment). Phase 1 data cutoff date 22-Jul-2019 for responses confirmed by BICR and 26-Aug-2021 for duration of treatment. Duration of Treatment (Phase 1 + Phase 2) N= 17 EXP-5 Phase 1 + 2 (N=17) Duration of Treatment (range in months) 0.9 – 30.7+ Patients remaining on treatment – n (%) 12 (71%) Patients with confirmed response Phase 1 + 2 (n=7) Duration of Treatment (range in months) 4.3+ – 30.7+ Patients with confirmed response remaining on treatment – n (%) 7 (100%)


Slide 17

NTRK+ TKI-Pretreated Advanced Solid Tumors: Preliminary Clinical Activity Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. *At time of the 26-Aug-2021 data cut off, 3 patients in Phase 2 EXP-6 had unconfirmed PR (uPR). Two uPRs have been confirmed since the 26-Aug-2021 data cut off and are included in the cORR; the third patient is on treatment awaiting a confirmatory scan. Phase 2: RECIST v1.1 assessed by Physician Assessment with a data cutoff date of 26-Aug-2021. Phase 1: RECIST v1.1  assessed by Blinded Independent Central Review (BICR) with data cutoff date of 22-Jul-2019 for patients with baseline measurable disease and ≥ 1 post-baseline scan. Phase 1 patients  treated at or above the Phase 2 recommended dose. Data updated since pre-recorded presentation at the AACR-NCI-EORTC conference. Overall Response (Phase 1 + Phase 2) N= 23 # Patient remains on treatment 1 patient not displayed due to discontinuing treatment prior to first post-baseline scan 1 patient not displayed due to target lesion measurement not performed at the post-baseline scan EXP-6 Phase 2 (N=22) Phase 1 + 2 (N=23) Confirmed ORR (cORR) (95% CI) 50%* (28 – 72) 48%* (27 – 69) Duration of Response (range in months) 0.9+ – 15.1 n=11 0.9+ – 15.1 n=11


Slide 18

NTRK+ TKI-Pretreated Advanced Solid Tumors with NTRK Resistance Mutations: Preliminary Clinical Activity Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. **At time of the 26-Aug-2021 data cut off, 3 patients in Phase 2 EXP-6 with a resistance mutation had unconfirmed PR (uPR). Two uPRs have been confirmed since the 26-Aug-2021 data cut off and are included in the cORR; the third patient is on treatment awaiting confirmatory scans. All resistance mutations were solvent front mutations and none were from Phase 1. Data updated since pre-recorded presentation at the AACR-NCI-EORTC conference. Overall Response (Phase 2) N= 13 EXP-6: Solvent Front Mutation Phase 2 (N=13) Confirmed ORR (cORR) (95% CI)     CR     PR 62%** (32 - 86) 1 (8%)   7 (54%) Duration of Response (range in months) 0.9+ – 13.7 n=8


Slide 19

NTRK+ TKI-Pretreated Advanced Solid Tumors: Duration of Treatment Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Phase 2 data cutoff date 26-Aug-2021 (responses confirmed by Physician Assessment). Phase 1 data cutoff date 22-Jul-2019 for responses confirmed by BICR and 26-Aug-2021 for duration of treatment. Duration of Treatment (Phase 1 + Phase 2) N= 23 EXP-6 Phase 1 + 2 (N=23) Duration of Treatment (range in months) 0.6 – 20.8 Patients remaining on treatment – n (%) 9 (39%) Patients with confirmed response Phase 1 + 2 (n=11) Duration of Treatment (range in months) 4.0+ - 20.8 Patients with confirmed response remaining on treatment – n (%) 7 (64%)


Slide 20

Safety Summary: Phase 1 and Phase 2 Combined  All Treated Patients (N=301)  All Treated Patients (N=301)  TEAEs (≥15% of patients)  TRAEs Adverse Events All Grades n (%) Grade 3 n (%) Grade 4 n (%) Grade 3 n (%) Grade 4 n (%) Dizziness 181 (60.1) 7 (2.3) 0 7 (2.3) 0 Dysgeusia 132 (43.9) 1 (0.3) 0 1 (0.3) 0 Constipation 101 (33.6) 1 (0.3) 0 0 0 Paraesthesia 87 (28.9) 3 (1.0) 0 3 (1.0) 0 Dyspnoeaa 84 (27.9) 18 (6.0) 3 (1.0) 1 (0.3) 0 Anaemia 82 (27.2) 24 (8.0) 1 (0.3) 10 (3.3) 0 Fatigue 73 (24.3) 5 (1.7) 0 2 (0.7) 0 Nausea 62 (20.6) 3 (1.0) 0 0 0 Muscular weakness 57 (18.9) 5 (1.7) 0 3 (1.0) 0 Ataxia 51 (16.9) 0 0 0 0 Repotrectinib was generally well tolerated Most TRAEs were Grade 1 or 2 The most commonly-reported TEAE remains low-grade dizziness (60%) 76% (138/181) were Grade 1 11 (4%) patients reported ataxia in the absence of dizziness No events of dizziness or ataxia led to treatment discontinuation Dose modifications due to TEAEs 27% with TEAEs that led to dose reduction 11% with TEAEs that led to drug discontinuation Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. 2 Grade 4 TRAEs of transient CPK increase and no Grade 5 TRAEs. TEAE = treatment-emergent adverse event; TRAE = treatment-related adverse event. Data cutoff date 26-Aug-2021. a One patient reported Grade 5 dyspnoea.


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Repotrectinib Regulatory Update For ROS1+ NSCLC, anticipated FDA meeting in 1H 2022 to discuss topline BICR results in at least 50 TKI-naïve and 50 TKI-pretreated patients with at least 6 months of follow-up For NTRK+ TKI-pretreated advanced solid tumors, Type B meeting with FDA anticipated in 1H 2022 to discuss next steps towards potential registration in this patient population BTD recently granted for the treatment of patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with 1 or 2 prior TRK TKIs, with or without prior chemotherapy, and have no satisfactory alternative treatments


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Repotrectinib Combinations in KRAS-Driven Tumors


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Inhibits JAK2, SRC and FAK Leads to suppression of STAT3 and AKT signaling, major mechanisms of resistance Demonstrated synergy with trametinib (MEK inhibitor) in mutant KRAS NSCLC, CRC and pancreatic cancer cell lines Demonstrated synergy with AMG510, inhibiting KRASG12C tumor cell proliferation, suppressing receptor tyrosine kinase upregulation, reducing KRASG12C tumor cell cytokine release Repotrectinib Selectivity Profile Potentially Expands Opportunity Beyond ROS1 and TRK for Combinations Repotrectinib in Preclinical Models Inhibited by Repotrectinib Note: Data presented at 2020 and 2021 annual AACR meetings. Authors: B. Murray, et al.


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Repotrectinib / Trametinib Combination Exhibits Greater Tumor Growth Inhibition in KRAS G12D Syngeneic and PDX Lung Cancer Models mLU6045 KRAS G12D Note: Data presented at 2021 annual AACR meeting. 1500 1000 500 0 Tumor Volume mm3 (SEM) 0 5 10 15 20 25 Days of Treatment Vehicle BID Repotrectinib 15 mg/kg BID Trametinib 1 mg/kg QD Repotrectinib 15 mg/kg BID + Trametinib 1 mg/kg QD Repotrectinib combination with trametinib is more effective than single-agent treatment in patient-derived KRAS mutant lung (KRAS G12D/V) and pancreatic (KRAS G12D/V/R) spheroid models Repotrectinib enhances trametinib efficacy in mutant KRAS G12D in vivo lung tumor models Overall, preclinical combination data suggest that a combination with repotrectinib may enhance trametinib potency and may improve durability of response by reversing or preventing acquired resistance **** ~2-fold increase in TGI **** p < 0.0001


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Repotrectinib combination shows a significant survival benefit in NSCLC KRASG12C xenograft model Builds on prior preclinical studies showing synergy with AMG510, inhibiting KRASG12C tumor cell proliferation, suppressing receptor tyrosine kinase upregulation, reducing KRASG12C tumor cell cytokine release Additional preclinical studies are on-going with AMG510 and other KRASG12C inhibitors Repotrectinib Enhances Survival with AMG510 in NSCLC KRASG12C Xenograft Tumor Model Note: Data presented at 2020 EORTC-NCI-AACR Symposium; Authors: B. Murray, et al Repotrectinib/AMG510, 30 mg/kg vs AMG510, 30 mg/kg, p=0.0138 H2122 Xenograft Model


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TRIDENT-2: Phase 1b/2 Study of Repotrectinib Combinations for the Treatment of KRAS Mutant Cancers, Currently in Dose Finding Key Subject Entry Criteria: KRAS mutant advanced cancer (KRAS mutation type(s) to be defined for each cohort) Measurable disease per RECIST v1.1 Asymptomatic CNS disease allowed ECOG 0-1 RP2D Cohort Dose Expansion (N ~ 50) Dose Level (DL1)¹ DL2 DL3 MTD Cohort Dose Finding (N ~ 18-24) Cohorts: Repotrectinib + trametinib in KRAS mutant G12D advanced solid tumors Dose Expansion Objectives: Primary: ORR Secondary: DOR, PFS, OS, IC-ORR, PK, Safety, QOL


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SHIELD-1: An Ongoing Phase 1 Study of Elzovantinib (TPX-0022) in Patients with Advanced Solid Tumors Harboring Genetic Alterations in MET


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Phase 1 SHIELD-1 Study of Elzovantinib (TPX-0022) in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET *Solid Tumors with MET Fusions or Oncogenic KD Mutations OR MET-amplified other than GI/NSCLC OR otherwise eligible for Cohorts I, III, or IV and >2 lines prior systemic therapy. BID, twice daily; CNS, central nervous system; CRC, colorectal cancer; GC, gastric cancer; GEJ, gastroesophageal junction; GI, gastrointestinal; HCC, hepatocellular carcinoma; KD, kinase domain; MET, mesenchymal-epithelial transition factor; MTD, maximum tolerated dose; NSCLC, non-small cell lung cancer; QD, once daily; RECIST v1.1, response evaluation criteria in solid tumors version 1.1; RP2D, recommended phase 2 dose. Population Adults with advanced solid tumors MET genetic alterations assessed by local testing (exon 14 deletion, amplification, fusion, or oncogenic kinase domain mutation) Asymptomatic CNS disease allowed Design 3+3 with expansion allowed at doses where clinical activity is observed Response evaluation by RECIST v1.1 Primary Objectives Evaluate safety/tolerability and determine MTD and RP2D Dose Finding Expansion Cohorts Dose Expansion NSCLC Exon 14 Deletion TKI-Naive GI (GC/GEJ, CRC, HCC) MET Amplified (GCN ≥ 10) TKI-Naive NSCLC Exon 14 Deletion TKI-Pretreated NSCLC MET Amplified (GCN ≥ 10) TKI-Naive NSCLC or GI (GC/GEJ, CRC, HCC) MET Amplified (GCN 5-9) TKI-Naive Other* TKI-Naive 40 mg QD 80 mg QD 120 mg QD 20 mg QD Titration Schedules: 80 mg QD (14 days)  120 mg QD 60 mg QD (14 days)  60 mg BID 40 mg QD (14 days)  40 mg BID 40 mg QD (14 days)  80 mg QD


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Elzovantinib was generally well tolerated Most common TEAE was dizziness, likely due to off target TRK inhibition Dose modifications due to TEAE 21 (38.9%) patients with TEAEs leading to dose reduction 3 (5.6%) patients with TEAEs leading to drug discontinuation 2 DLTs at 120 mg QD* All Grade peripheral edema in 11 (20.4%) patients (no Grade ≥ 3 event) No ILD/pneumonitis of any Grade No related Grade ≥ 3 ALT/AST elevation Preliminary Safety Summary All Treated Patients (N=54) TEAEs (≥15% of patients) TRAEs Adverse Events All Grades Grades≥3 All Grades Grades≥3^ n (%) n (%) n (%) n (%) Dizziness 35 (64.8) 2 (3.7) 31 (57.4) 1 (1.9) Constipation 18 (33.3) 1 (1.9) 3 (5.6) - Fatigue 17 (31.5) 3 (5.6) 12 (22.2) 2 (3.7) Lipase increased 17 (31.5) 3 (5.6) 17 (31.5) 2 (3.7) Anaemia 16 (29.6) 5 (9.3) 2 (3.7) - Amylase increased 15 (27.8) 1 (1.9) 13 (24.1) 1 (1.9) Nausea 12 (22.2) 1 (1.9) 7 (13.0) - Vomiting 12 (22.2) 3 (5.6) 4 (7.4) - Oedema peripheral 11 (20.4) - 9 (16.7) - Abdominal pain 10 (18.5) 2 (3.7) 1 (1.9) - Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Data cut-off date August 23, 2021. ^ Other reported Grade 3 TRAEs are: asthenia, blood creatine phosphokinase increased, delirium, vertigo, vestibular disorder. No Grade 4 or 5 TRAEs. * Grade 3 vertigo and Grade 2 dizziness. ALT, alanine transaminase; AST, aspartate transaminase; BID, twice daily; DLT, dose-limiting toxicity; ILD, interstitial lung disease; QD, once daily; TEAE, treatment emergent adverse event; TRAE, treatment related adverse event.


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Preliminary Efficacy by Investigator Assessment Efficacy Outcomes TKI-Naïve Efficacy Evaluable Patients (N=32) Efficacy Outcomes NSCLC (N=11) GC/GEJ (N=9) Other Tumor Types (N=12) Best Overall Response PR – n (%) 4 (36) 3 (33) 1 (8) SD – n (%) 3 (27) 3 (33) 7 (58) PD – n (%) 4 (36) 3 (33) 4 (33) cORR 36% 33% 8% CBR 64% 67% 67% Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Data cut-off date August 23, 2021. CBR = PR + SD CBR, clinical benefit rate; cORR, confirmed objective response rate; GC/GEJ, gastric cancer/gastroesophageal junction; NSCLC, non-small cell lung cancer; PD, progressive disease; PR, partial response; SD, stable disease. TKI Pre-treated Efficacy Evaluable (N=14) Among 14 TKI-pretreated efficacy evaluable patients (13 NSCLC and 1 liver cancer), 36% received at least 5 lines of prior therapy (median: 3; range: 1-6), 7 NSCLC patients achieved SD as best overall response for a CBR of 54% in NSCLC.


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Preliminary Clinical Activity by Investigator Assessment TKI-Naïve NSCLC and GC/GEJ Efficacy Evaluable Subjects (n=20) ↑ ∞ # Patient remains on treatment ↑ Patient has presence of both MET fusion and MET amplification ∞ uPR followed by PD Deepening response from 15Oct2020 data Preliminary Efficacy TKI-Naïve Efficacy Evaluable NSCLC GC/GEJ All Dose Levels, N 11 9 cORR (95% CI) 36% (11 - 69) 33% (7 - 70) CBR (95% CI) 64% (31 - 89) 67% (30 - 93) Note:  95% patients received prior Chemo/IO therapy DOR for 7 PRs were 15+, 12.9+, 9.2+, 5.6+, 5.6+, 5.2, and 1.8+ months MET amplification: 4 PRs (GCN: 7, 12, 14, and 25); 8 non-responders (GCN: n=6 had <10; n=1 had ≥6; n=1 had >13) Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Data cut-off date August 23, 2021 CBR, clinical benefit rate; cORR, confirmed objective response rate; DOR, duration of response; GC/GEJ, gastric cancer/gastroesophageal junction adenocarcinoma; GCN, gene copy number; IO, immunotherapy; NSCLC, non-small cell lung cancer; PD, progressive disease; RP2D, recommended phase 2 dose.


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Duration of Treatment TKI-Naïve NSCLC and GC/GEJ Efficacy Evaluable Subjects (n=20) Duration of Treatment NSCLC (n=11): 3.4 weeks to 78.6+ weeks GC/GEJ (n=9) : 4.4 weeks to 68.1+ weeks Note: Presented at AACR-NCI-EORTC Conference in Oct-2021. Data cut-off date August 23, 2021 GC/GEJ, gastric cancer/gastroesophageal junction; NSCLC, non-small cell lung cancer.


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Elzovantinib Regulatory Update Recent End of Phase 1 meeting with the FDA focused on next steps in patients with NSCLC In initial feedback, FDA recommended exploring an intermediate dose level using the QD titration to BID dosing strategy in at least 6 to 10 patients prior to starting the Phase 2 portion of the study Plan to enroll at least 6 to 10 patients at 60 mg QD (14 days)  60 mg BID in Phase 1 Plan to revise SHIELD-1 into a potentially registrational Phase 1/2 study and initiate the Phase 2 portion in 2022, pending FDA feedback on data from the intermediate dose level FDA feedback focused on gastric/gastroesophageal junction cancer (GEJ) is pending Plan to initiate the SHIELD-2 combination study with an EGFR targeted therapy in 2022, pending filing of an IND application by the FDA


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SWORD-1: An Ongoing Phase 1 Study of TPX-0046 in Patients with Advanced Solid Tumors Harboring RET Fusion or Mutation


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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


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Phase 1/2 SWORD-1 Study Design of TPX-0046 in Patients with Advanced Solid Tumors Harboring RET Fusion or Mutation, Currently in Dose Finding * Additional doses and/or schedules may be explored. 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 Phase 1 Dose Escalation* Dose evaluation ongoing 10 mg QD 20 mg QD 10 mg BID 30 mg QD 20 mg  30 mg QD 20 mg BID 20 mg  40 mg QD Phase 1 Dose Expansion (n~90) RET Fusion+ NSCLC RET TKI-Naïve RET Fusion+ NSCLC 1 Prior RET TKI RET Mutation+ MTC RET TKI-Naïve RET Mutation+ MTC 1 Prior RET TKI RET Fusion+ Non-NSCLC RET+ NSCLC or MTC >1 Prior RET TKI or >1 Line of Additional Systemic Therapy RP2D 20 mg QD  20 mg BID


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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) TPX-0046: Preliminary Safety Summary Note: Data cutoff of 10-Mar-2021. * DLT was reported as treatment related Grade 2 gait disturbance. TEAE: treatment emergent adverse event; TRAE: treatment related adverse event; MTD: maximum tolerated dose; DLT: dose-limiting toxicity All Treated Patients (N=21) TEAEs (≥20% of patients) TRAEs All Grades Grades≥3 All Grades Grades≥3 Adverse Events n (%) n (%) n (%) n (%) Dizziness 9 (42.9) 1 (4.8) 7 (33.3) 1 (4.8) Fatigue 8 (38.1) 2 (9.5) 5 (23.8) 1 (4.8) Alkaline phosphatase increased 6 (28.6) 1 (4.8) - - Constipation 6 (28.6) 1 (4.8) 2 (9.5) - Decreased appetite 6 (28.6) - - - Dry mouth 6 (28.6) - 4 (19.0) - Hyperphosphataemia 6 (28.6) - 4 (19.0) - Lipase increased 6 (28.6) 1 (4.8) 2 (9.5) - Alanine aminotransferase increased 5 (23.8) - 1 (4.8) - Dehydration 5 (23.8) 1 (4.8) - - Muscular weakness 5 (23.8) 1 (4.8) 2 (9.5) -


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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 TPX-0046: Preliminary Efficacy by Investigator Assessment Note: Data cutoff of 10-Mar-2021. TKI: tyrosine kinase inhibitor; NSCLC: non-small cell lung cancer; MTC: medullary thyroid carcinoma; DOR: duration of response # Patients remained on treatment


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TPX-0131: A Next Generation ALK Inhibitor


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TPX-0131: Highly Potent, CNS Penetrant ALK Inhibitor Note: Data presented at 2021 AACR Conference. ¹ Shaw A et al., J Clin Oncol 37:1370-1379. TPX-0131 Differentiation Potently inhibit WT ALK, and multiple resistant mutations (solvent front, gatekeeper and compound) Solvent front mutation G1202R reported in ~42% of patient biopsies with a resistance mutation¹ Target Population Pretreated ALK+ NSCLC and other solid tumors Development Stage Phase 1/2 FORGE-1 study ongoing Cell Proliferation IC50 Values (nM) Inhibitor ALK WT ALK G1202R ALK L1196M ALK G1202R/L1196M ALK G1202R/L1198F ALK G1202R/C1156Y ALK L1196M/L1198F TPX-0131 0.4 0.2 0.5 0.7 <0.2 0.2 <0.2 Alectinib 7.4 2690 50 >10000 3000 2420 2250 Brigatinib 12 188 21 1100 2040 810 253 Ceritinib 3.9 329 5.4 1260 2010 1300 1410 Lorlatinib 0.8 52 38 4780 1710 521 1310 Crizotinib 50 434 274 808 188 745 252


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Phase 1/2 FORGE-1 Study of TPX-0131 in Patients with ALK+ NSCLC, Currently in Dose Finding Study Endpoints: Primary: Evaluate safety / tolerability and determine maximum tolerated dose (MTD) and / or recommended Phase 2 dose (RP2D) Secondary: Objective Response Rate (ORR) by RECIST 1.1 Phase 1 Dose Escalation 3+3 design with expansion allowed at doses where clinical activity is observed Locally advanced or metastatic TKI-pretreated ALK+ NSCLC Asymptomatic CNS metastases allowed RP2D Dose Level (DL1) DL2 DL3 MTD Phase 2 Expansion (N=180)


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Discovery Programs


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PAK1/4 KRAS G12D Key downstream effectors RAF-MEK-ERK Established oncogenic driver Multi-tumor opportunity in subsets of pancreatic cancer, colorectal cancer and NSCLC Discovery Program Focused on Dysregulated GTPase Signaling, Which Plays a Central Role in Cancer Promotion and Progression Note: Figure adapted from Brito et al., Front. Cell Dev. Biol., 23, 2020. Focus: Targets that play large roles in aberrant GTPase activity and signaling known to drive genomically defined cancers Approach: Fragment and structure-based drug design Minimum Selection Criteria: High unmet medical need, strong biologic rationale, potential market opportunity Goal: Nominate 2 development candidates in 2H 2022, and at least 1 IND annually beginning in 2023 p21 Activated Kinase Activated by upstream GTPases RAC1 and Rho Key RAS signaling effectors Activates key signaling nodes (MEK, AKT, β-catenin, cyclin D) Preclinically validated Goal is isoform selective agent of PAK1 and PAK4 Multi-tumor opportunity in subsets of breast, ovarian, melanoma, and NSCLC


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Financial Highlights


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Financial Highlights As of June 30, 2021 NASDAQ TPTX Cash, Cash Equivalents, and Marketable Securities $1.1B Basic Shares Outstanding 49.4M Fully Diluted Shares Outstanding 55.2M


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October 2021 Next-Generation Precision Oncology Medicines Company Overview