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


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 


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 


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 


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 


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 


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. 


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 


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 


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 


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 


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  


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 


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 


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