Black Diamond Therapeutics Presents Phase 1 Pharmacokinetic, Safety, and Preliminary Efficacy Data of BDTX-189 in Advanced Solid Tumors Harboring EGFR or HER2 Alterations Once-daily (QD) dose escalation completed; pharma

Diamond Therapeutics Presents Phase 1 Pharmacokinetic, Safety, and

Preliminary Efficacy Data of BDTX-189 in Advanced Solid Tumors Harboring

EGFR or HER2 Alterations

Once-daily (QD) dose

escalation completed; pharmacokinetic (PK) profile consistent with design principles and preclinical predictions

Generally well-tolerated

with medically manageable toxicities observed; safety profile compares favorably in the context of other agents in the class; preliminary

recommended Phase 2 dose (RP2D) selected for the QD regimen

Preliminary anti-cancer

activity observed in heavily pre-treated patients (prior EGFR/HER2-directed and/or I/O agents) in a variety of tumor types and genomic

alterations in EGFR or HER2, including confirmed partial responses

webcast to be held today at 6:00 PM ET

Mass. and NEW YORK, May 19, 2021 -

Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small

molecule, MasterKey therapies, today announced initial data from the Phase 1 dose-escalation portion of the MasterKey-01 trial of BDTX-189

in patients with advanced solid tumors harboring any one of more than 48 oncogenic alterations in the epidermal growth factor receptor

(EGFR) and human epidermal growth factor receptor 2 (HER2) oncogenes. These data provide early proof-of-concept for BDTX-189, including

evidence of anti-cancer activity and a safety profile that is in-line with the Company's preclinical expectations. The data announced

today will be presented in poster presentations at the upcoming 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, taking

place June 4-8, 2021.

encouraging Phase 1 safety and anti-cancer activity data provide early proof-of-concept for BDTX-189 as a differentiated MasterKey inhibitor

of undrugged oncogenic mutants of EGFR, including EGFR Exon 20 insertion mutations and oncogenic mutants of HER2," said Rachel Humphrey,

M.D., Chief Medical Officer of Black Diamond Therapeutics. "We look forward to the continued advancement of BDTX-189 through clinical

development and remain on track to initiate the potentially pivotal Phase 2 portion of the MasterKey-01 trial in the second half of 2021."

initial data suggest BDTX-189 may provide meaningful clinical benefit to patients with advanced solid tumors, including those with

allosteric EGFR and HER2 mutations," said Alison Schram, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center.

"The favorable tolerability profile demonstrated thus far supports the potential of BDTX-189 to address the

unmet need in this patient population, for which there are no currently approved targeted therapies and where other in-clinic agents

are limited by toxicity."

Part A Dose-Escalation Study Design

a Phase 1, first-in-human, open-label dose escalation study, comprised of initial single-patient, accelerated titration cohorts followed

by multiple-patient cohorts utilizing a Bayesian Optimal Interval (BOIN) design. Part A is designed to determine the recommended Phase

2 dose and schedule for the QD and twice-daily (BID) regimens in patients with solid tumors with an allosteric HER2 or HER3 mutation;

EGFR or HER2 Exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or EGFR Exon 19 deletion or L858R mutation.

data cut-off date of April 2, 2021, 55 patients from the QD regimen were dosed across the dosing range, 25-400 mg QD fasting (n = 12),

800 mg QD fasting (n = 21), 800 mg QD non-fasting (n = 9), 1000 mg QD fasting (n = 7), and 1200 mg QD fasting (n = 6). The dose-escalation

portion successfully enrolled patients with a broad range of tumor types and genomic alterations. Tumor types enrolled included non-small

cell lung cancer (NSCLC), breast, colorectal (CRC), ovary, biliary, pancreas, cervical, cancer of unknown primary, kidney, salivary, prostate,

signet ring cell, liver, and bladder. Genomic alterations enrolled included HER2 amplification and the following mutations: allosteric

HER2, EGFR Exon 20 insertion, HER2 Exon 20 insertion, EGFR Exon 19 del./L858R, and HER3.

for the BDTX-189 QD regimen demonstrated dose-dependent increases in exposure up to 800 mg QD, achieving the predicted efficacious exposure

at 800 mg QD. BDTX-189 was rapidly absorbed, with a short elimination half-life of 1.3-4.4 hours, consistent with preclinical predictions.

No apparent accumulation or change in exposure at steady state was observed.

demonstrated a favorable tolerability profile, with no dose-limiting toxicities at doses of 800 mg QD fasting and non-fasting

in the dose-escalation cohorts. 800 mg non-fasting was selected as the preliminary RP2D for the QD regimen.

most common drug-related adverse events were gastrointestinal in nature, the majority of which were low grade and generally

medically manageable. At 800 mg QD fasted or non-fasted (n = 30), the most common drug-related adverse events were diarrhea (50%, 7%

Gr3), nausea (50%, 7% Gr3), vomiting (30%, 3% Gr3), ALT increased (20%, 10% Gr3), AST increased (13%, 3% Gr3), fatigue (20%, 0%

Gr3), skin disorders (13%, 0% Gr3), and decreased appetite (10%, 0% Gr3).

pre-treated patient population, including patients who had received prior EGFR/HER2 tyrosine kinase inhibitors (TKI), evidence of anti-cancer

activity was observed. Among all cancer type/genomic alteration pairs, two had three RECIST-evaluable patients dosed at 800

mg QD: NSCLC harboring either EGFR Exon 20 mutations (n = 3) or HER2 Exon 20 mutations (n = 3). In the separate group of patients with

solid tumors harboring HER2-amplification, six patients dosed at 800 mg QD were evaluable by RECIST.

incredibly encouraged by the rapid progress of the MasterKey-01 study and promising proof-of-concept data for BDTX-189. These

preliminary data support the differentiated profile of BDTX-189 as a MasterKey inhibitor of diverse oncogenic alterations in EGFR

and HER2, as well as initial validation of Black Diamond's proprietary MAP drug discovery engine and MasterKey approach to

drug development," said David M. Epstein, President and Chief Executive Officer of Black Diamond Therapeutics.

"We'd like to thank all the patients, their families, and their caregivers for participating in this

is continuing to dose patients in the ongoing QD dose-escalation portion and the food effect cohort, as well as enrolling and dosing patients

in the BID dose-escalation portion. The Company will initiate the safety expansion cohort ahead of the Phase 2 portion of the MasterKey-01

study, which remains on track for initiation in the second half of 2021.

is a Phase 2, open-label, multi-center study designed to determine anti-cancer activity and safety in adult patients with solid

tumors harboring an allosteric HER2 mutation or EGFR or HER2 Exon 20 insertion mutation. This portion of the trial will enroll

patients in focused tumor/mutation cohorts and is designed to be potentially pivotal. Additionally, based on early proof-of-concept

data, Black Diamond is exploring the potential for further clinical development in the HER2-amplified setting.

announced today will be presented in poster presentations at the upcoming ASCO meeting:

Title: Safety and Preliminary

Efficacy from the Phase 1 Portion of MasterKey-01: A First-in-Human Dose-Escalation Study to Determine the Recommended Phase 2 Dose (RP2D),

Pharmacokinetics (PK), and Preliminary Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB mutations, in Patients with Advanced

Session Type: Poster Session

Session: Developmental Therapeutics

- Molecularly Targeted Agents and Tumor Biology

Date and Time: Friday, June 4,

Title: Clinical pharmacokinetics

of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study

Session Type: Poster Session

Session: Developmental Therapeutics

- Molecularly Targeted Agents and Tumor Biology

Date and Time: Friday, June 4,

with today's announcement, Black Diamond's management team will host a conference call and live audio webcast at 6:00 PM ET

today, Wednesday, May 19, 2021.

audio webcast and accompanying slides may be accessed through the Events page in the Investors section of the Company's website at www.blackdiamondtherapeutics.com. Alternatively, the conference call may be accessed as follows:

Dial-in Number: 1-833-730-3983

Dial-in Number: 1-720-405-2158

unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company's

BDTX-189 is an orally available, irreversible, and ATP competitive small molecule inhibitor that is designed to block the function

of a family of oncogenic epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) proteins across a

range of tumor types. BDTX-189 is designed as a MasterKey inhibitor targeting a family of previously undrugged and functionally similar

oncogenic mutations in a tumor-agnostic manner. These mutations include extracellular domain allosteric mutations of HER2, as well as

EGFR and HER2 kinase domain Exon 20 insertions, and additional activating oncogenic drivers of EGFR and HER2. BDTX-189 is also designed

to spare normal, or wild-type, EGFR, which we believe has the potential to improve upon the toxicity profiles of current EGFR/HER2 kinase

inhibitors. Currently, there are no medicines approved by the U.S. Food and Drug Administration (FDA) to target all of these oncogenic

mutations with a single therapy.

BDTX-189 is currently being evaluated in a Phase

1/2 clinical trial (MasterKey-01) in adult patients with advanced solid tumors expressing a range of alterations of EGFR and HER2 receptors,

including oncogenic MasterKey mutations, HER2-WT amplification, HER3 mutation, EGFR Exon 19 deletion, and L858R mutation who have no standard

therapy available or for whom standard therapy is considered unsuitable or intolerable. In July 2020, the FDA granted Fast Track designation

to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric HER2 mutation or an EGFR or HER2 Exon 20 insertion

mutation who have progressed following prior treatment and who have no satisfactory treatment options.

About Black Diamond Therapeutics