On May 13, 2024 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical stage biopharmaceutical company developing a portfolio of small molecule product candidates to address serious diseases, including oncology and obesity, reported financial results for the first quarter ended March 31, 2024 and provided corporate updates (Press release, Terns Pharmaceuticals, MAY 13, 2024, View Source [SID1234643157]).

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"We continue to execute our strategy and make important progress on our pipeline of potential best-in-class small molecule therapies as we prepare for key data readouts from our two lead programs," said Amy Burroughs, chief executive officer of Terns, "We look forward to reporting both interim dose escalation data from the ongoing Phase 1 CARDINAL trial of TERN-701 in CML and top-line data from the Phase 1 trial of TERN-601 in obesity in the second half of this year."

"We are particularly pleased with the recent findings from our Phase 1 study of TERN-701 in healthy volunteers, which showed lack of food effect and supports once-daily dosing. This represents a key potential differentiator as the only approved allosteric BCR-ABL inhibitor requires three hours of fasting with each dose and twice-daily dosing in multiple clinical settings," added Ms. Burroughs.

Recent Pipeline Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL inhibitor for chronic myeloid leukemia (CML)

•
Terns’ Phase 1 CARDINAL trial of TERN-701 in CML is ongoing and interim data from initial CARDINAL dose escalation cohorts are expected in the second half of 2024
o
CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK), and efficacy of TERN-701 in patients with previously treated CML
•
In April, Terns announced findings from a concurrent Phase 1 PK study of TERN-701 in U.S. healthy volunteers, which indicated TERN-701 can be administered once-daily (QD) with or without food at doses that achieve clinically efficacious exposures
•
In March 2024, the United States Food and Drug Administration (FDA) granted Orphan Drug Designation for TERN-701 for the treatment of CML
•
Terns plans to host a TERN-701-focused virtual key opinion leader (KOL) event in mid-2024

TERN-601: Oral, small molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

•
Phase 1 first-in-human clinical trial of Terns’ lead oral GLP-1 receptor agonist in obese and overweight participants is progressing
•
The multiple ascending dose (MAD) portion of the study is underway, testing once-daily administration of TERN-601, and is on track to report top-line 28-day weight loss data in the second half of 2024
•
Preliminary safety findings from the ongoing, blinded Phase 1 SAD/MAD study have been unremarkable to date with no observations of liver enzyme elevations, drug induced liver injury or discontinuations due to treatment-related adverse events

TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist

•
Terns continues to evaluate opportunities for TERN-501 in metabolic diseases
o
Based on non-clinical studies, THR-β is an orthogonal mechanism to GLP-1, potentially providing broader metabolic and liver benefits in addition to increased weight loss
o
Non-clinical data suggests that TERN-501 may augment the weight loss effects of a GLP-1 receptor agonist, as demonstrated in a diet-induced obese mouse model

TERN-800 Series: Oral, small molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators

•
Discovery efforts are ongoing for small molecule GIPR modulators for obesity, which have the potential for combination with GLP-1 receptor agonists, such as TERN-601
•
Terns is prioritizing its discovery efforts on nominating a GIPR antagonist development candidate based on in-house discoveries and growing scientific rationale supporting the potential of GLP-1 agonist/GIPR antagonist combinations for obesity

Corporate Updates

•
In April 2024, Terns announced the appointment of Melita Sun Jung as chief business officer of Terns
•
In May 2024, Terns announced the appointment of Scott Harris as chief development officer and the upcoming departure of Erin Quirk, M.D., president, head of research and development

First Quarter 2024 Financial Results

Cash Position: As of March 31, 2024, cash, cash equivalents and marketable securities were $240.7 million, as compared with $263.4 million as of December 31, 2023. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2026.

Research and Development (R&D) Expenses: R&D expenses were $18.6 million for the quarter ended March 31, 2024, as compared with $17.1 million for the quarter ended March 31, 2023.

General and Administrative (G&A) Expenses: G&A expenses were $6.9 million for the quarter ended March 31, 2024, as compared with $7.1 million for the quarter ended March 31, 2023.

Net Loss: Net loss was $22.4 million for the quarter ended March 31, 2024, as compared with $21.5 million for the quarter ended March 31, 2023.

Financial Tables

Terns Pharmaceuticals, Inc.

Condensed Consolidated Statements of Operations

(Unaudited; in thousands except share and per share amounts)

Three Months Ended March 31,

2024

2023

Operating expenses:

Research and development

$

18,587

$

17,056

General and administrative

6,859

7,101

Total operating expenses

25,446

24,157

Loss from operations

(25,446

)

(24,157

)

Interest income

3,182

2,693

Other expense, net

(12

)

(4

)

Loss before income taxes

(22,276

)

(21,468

)

Income tax expense

(97

)

(60

)

Net loss

$

(22,373

)

$

(21,528

)

Net loss per share, basic and diluted

$

(0.30

)

$

(0.31

)

Weighted average common stock outstanding, basic and diluted

74,399,378

69,778,420

Terns Pharmaceuticals, Inc.

Selected Balance Sheet Data

(Unaudited; in thousands)

March 31, 2024

December 31, 2023

Cash, cash equivalents and marketable securities

$

240,654

$

263,440

Total assets

246,766

268,517

Total liabilities

10,046

13,150

Total stockholders’ equity

236,720

255,367

On May 13, 2024 Ajax Therapeutics, Inc., a biopharmaceutical company developing next generation JAK inhibitors for patients with myeloproliferative neoplasms (MPNs), reported that it has received clearance for its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1clinical study of AJ1‑11095, a first-in-class Type II JAK2 inhibitor, for the treatment of patients with myelofibrosis (Press release, Ajax Therapeutics, MAY 13, 2024, View Source [SID1234643179]).

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"We are thrilled to obtain clearance to advance AJ1-11095 into the clinic and excited to bring this innovative new medicine to patients with myelofibrosis," said Martin Vogelbaum, co-founder and CEO of Ajax Therapeutics. "This is an important milestone for our company and our first program to enter the clinic and the first clinical study to ever evaluate a Type II JAK2 inhibitor in patients."

"We look forward to the clinical development of AJ1-11095 in myelofibrosis and to initiating our Phase 1 dose escalation study, AJX-101, later this year," said David Steensma, MD, FACP, Chief Medical Officer at Ajax. "As a first-in-class therapy with a unique mechanism as a Type II inhibitor of JAK2, AJ1-11095 was developed to provide a much-needed new treatment for patients with myelofibrosis by offering the potential for improved efficacy with disease modifying effects compared to existing therapies."

About AJ1-11095

AJ1-11095 was designed by Ajax, through our collaboration with Schrödinger, to be a next generation JAK2 inhibitor by using structure-based drug design and computational methods at scale to selectively bind the Type II conformation of the JAK2 kinase and to provide greater efficacy with disease modification compared to all currently approved JAK2 inhibitors which bind the Type I conformation of JAK2. Additionally, AJ1-11095 has been shown in preclinical studies to reverse marrow fibrosis, reduce mutant allele burden and maintain efficacy against MPN cells that become resistant to chronic Type I JAK2 inhibition.

About Myelofibrosis

Myelofibrosis (MF) is a rare blood cancer that affects approximately 20,000 patients in the United States. The disease is characterized by spleen enlargement, scarring (fibrosis) in the bone marrow, progressive anemia, and debilitating symptoms, such as fatigue, night sweats, itching, and abdominal discomfort, which can impair a patient’s’ quality of life. The most widely used treatment for MF patients are Type I JAK2 inhibitors which can reduce spleen size and provide symptomatic improvement but have little effect on the underlying cause of disease. Over time, most MF patients stop Type I JAK2 inhibitor therapy. The most common causes for treatment discontinuation include a lack of benefit or loss of response, adverse events, and disease progression, leaving significant unmet treatment needs for these patients.

On May 13, 2024 Barinthus Biotherapeutics plc (NASDAQ: BRNS), a clinical-stage biopharmaceutical company developing novel T cell immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases, autoimmunity, and cancer, reported its financial results for the first quarter of 2024 and provided an overview of the Company’s progress (Press release, Barinthus Biotherapeutics, MAY 13, 2024, View Source [SID1234643119]).

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"So far in 2024 we have continued to make strides across our programs. Notably, we received clearance from the FDA on an IND to progress VTP-1000 in a first in human clinical trial in celiac disease, as well as clearance from the Australian Ethics Committee on this trial. We expect to begin our Phase 1 trial of VTP-1000 in participants with celiac disease in the coming months. Additionally, we reported topline final data from the Phase 1b/2 trial of VTP-200 in participants with persistent high-risk (hr) human papillomavirus (HPV) infections," said Bill Enright, Chief Executive Officer of Barinthus Bio. "Looking ahead to Q2, we will present additional interim data from our VTP-300 hepatitis B trials at the European Association for the Study of the Liver (EASL) Congress in June. This follows the encouraging data presented at The American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting in November last year.

We will also welcome Dr. Leon Hooftman as our new Chief Medical Officer in June and look forward to him supporting the growth of our robust pipeline and programs."
Recent Corporate Developments
Clinical developments
•VTP-1000 (Celiac Disease): In April 2024, we received clearance from the U.S. FDA on an Investigational New Drug (IND) application, as well as from the Australian regulatory authorities, to progress VTP-1000 in a first in human clinical trial in celiac disease. GLU001 is a randomized, placebo-controlled Phase 1 trial with a controlled gluten challenge to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000 in adults with celiac disease. The study is designed in two parts; a single ascending dose part followed by a multiple ascending dose part, each randomized and placebo-controlled with three dose levels. The primary endpoint is assessment of the safety and tolerability of single and multiple dosing, and determination of a dose and schedule for further investigation. The trial also aims to demonstrate proof-of-principle of induction of immune tolerance and early proof-of-concept for VTP-1000, as a potential treatment for celiac disease, based on assessment of pharmacodynamics and preliminary efficacy determined by means of a controlled gluten challenge.

•VTP-200 (HPV): In April 2024, we announced topline final data from the APOLLO trial, (also known as HPV001) a Phase 1b/2 dose-ranging study of VTP-200 in women with low-grade cervical lesions associated with persistent hrHPV infection. The APOLLO study met its primary safety endpoint, demonstrating that VTP-200 was generally well-tolerated and was administered with no treatment-related grade 3 or higher unsolicited adverse events (AEs) and no treatment-related serious AEs. Positive trends in clearance rate for both hrHPV (60%, Group 2) and cervical lesions (67%, Groups 2 and 5), were observed in the groups receiving the highest ChAdOx dose. Pooled data from the five different active dose groups demonstrated no statistically significant improvement in either hrHPV or cervical lesion clearance in comparison to the placebo group.
•VTP-300 (HBV): In April 2024, abstracts on interim data from HBV003 and AB-729-202 were accepted for presentation at the upcoming EASL Congress in Milan, Italy, June 5-8, 2024.

Management Team

•On May 1, 2024, we announced the appointment of Dr. Leon Hooftman as Chief Medical Officer. Dr. Hooftman will join the company on June 3, 2024, and brings significant drug development expertise across a broad array of therapeutic areas including immunology, autoimmunity, hematology, oncology and infectious diseases.

Upcoming Milestones
•In the second quarter of 2024, the Company expects to:
◦VTP-300 (HBV): Present interim data from HBV003, our Phase 2b trial evaluating additional dosing of VTP-300 and timing of PD-1 inhibition, in participants with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NUC) therapy at the EASL Congress in June.
◦VTP-300 (HBV): Announce interim data from the Phase 2a AB-729-202 clinical trial evaluating the combination of VTP-300 and Arbutus’ imdusiran, in participants with CHB on NUC therapy following presentation at the EASL Congress in June.
•In the third quarter of 2024, the Company expects to:
◦VTP-1000 (Celiac Disease): Dose the first patient in GLU001, a randomized, placebo-controlled Phase 1 trial with a controlled gluten challenge to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000 in adults with celiac disease. This timing update is based on the latest feasibility and expected site set-up timelines.
First Quarter 2024 Financial Highlights
•Cash position: As of March 31, 2024, cash, cash equivalents and restricted cash was $130.0 million, compared to $142.1 million as of December 31, 2023. The cash used in operating activities was $11.8 million in the first quarter of 2024, primarily resulting from development of our pipeline and ongoing clinical trials. Based on current research and development plans, the Company expects its cash runway to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2025.
•Revenue: Revenue was nil in the first quarter of 2024 compared to $0.5 million in the first quarter of 2023 and was due to no commercial sales of Vaxzevria by AstraZeneca in 2024.
•Research and development expenses: Research and development expenses were $11.1 million in the first quarter of 2024 compared to $9.8 million in the first quarter of 2023, with the increase mainly attributable to hiring of personnel and increased costs related to the advancement of our programs. The quarter-on-quarter R&D expense per program is outlined in the following table.

Year ended Three months ended March 31, 2024 Three months ended March 31, 2023 Change
$000 $000 $000
Direct research and development expenses by program:
VTP-200 HPV $ 1,253 $ 1,338 $ (85)
VTP-300 HBV 1,913 2,118 (205)
VTP-500 MERS1
172 — 172
VTP-600 NSCLC2
164 275 (111)
VTP-850 Prostate cancer 178 215 (37)
VTP-1000 Celiac 1,374 1,572 (198)
Other and earlier stage programs3
784 280 504
Total direct research and development expenses $ 5,838 $ 5,798 $ 40
Indirect research and development expenses:
Personnel-related (including share-based compensation) 4,335 3,601 734
Facility related 390 371 19
Other indirect costs 562 44 518
Total indirect research and development expenses 5,287 4,016 1,271
Total research and development expense $ 11,125 $ 9,814 $ 1,311

1The development of VTP-500 is funded pursuant to an agreement with the Coalition for Epidemic Preparedness Innovations (CEPI).
2The VTP-600 NSCLC Phase 1/2a trial is sponsored by Cancer Research UK.
3Research and development expenses related to VTP-1100 HPV Cancer were previously included with VTP-1000 Celiac but are now included in ‘Other and earlier stage programs’ because we are focusing resources on other clinical programs and deferring the IND application for VTP-1100 in HPV cancer.
•General and administrative expenses: General and administrative expenses were $6.0 million in the first quarter of 2024, compared to $12.1 million in the first quarter of 2023. The decrease of $6.1 million relates primarily to a gain of $1.2 million on foreign exchange for the first quarter of 2024, compared to a loss of $3.5 million for the first quarter of 2023, a decrease in personnel expenses, including share-based payment charges of $0.8 million, primarily due to a reduction in non-cash share-based payment charges, and a decrease in insurance costs of $0.9 million due to a reduction in insurance premiums.
•Net loss: For the first quarter of 2024, the Company generated a net loss attributable to its shareholders of $15.5 million, or $(0.40) per share on both basic and fully diluted bases, compared to a net loss attributable to its shareholders of $18.2 million, or $(0.48) per share on both basic and fully diluted bases in the first quarter of 2023.

On May 13, 2024 Genmab A/S (Nasdaq: GMAB). On March 15, 2024, Genmab reported the initiation of a share buy-back program to repurchase up to DKK 3.5 billion worth of shares (Press release, Genmab, MAY 13, 2024, View Source [SID1234643141]).
The share buy-back program is expected to be completed no later than December 16, 2024.

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The following transactions were executed under the program from May 6, 2024 to May 10, 2024:

Trading Platform No. of shares Average price (DKK) Total value (DKK)
Accumulated through
last announcement 689,510 1,393,154,997.08
May 6, 2024 XCSE
CEUX
AQEU
TQEX
Total 0 0.00 0.00
May 7, 2024 XCSE 0 0
CEUX 35 1,998.00
AQEU 0 0
TQEX 0 0
Total 35 1,998.00 69,930.00
May 8, 2024 XCSE 28 2,013.00
CEUX 55 2,015.45
AQEU 0 0
TQEX 37 2,002.00
Total 120 2,010.73 241,288.00
May 9, 2024 XCSE
CEUX
AQEU
TQEX
Total 0 0.00 0.00
May 10, 2024 XCSE
CEUX
AQEU
TQEX
Total 0 0.00 0.00
Total 155 311,218.00
Accumulated under the program 689,665 1,393,466,215.08

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 1,538,803 shares as treasury shares, corresponding to 2.33% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 22 dated March 15, 2024.

On May 13, 2024 Think Bioscience ("Think"), a Boulder-based synthetic biology company focused on developing small-molecule therapeutics that target "undruggable" proteins, reported a $6M Seed Expansion (Press release, Think Bioscience, MAY 13, 2024, View Source;utm_medium=rss&utm_campaign=think-bioscience-extends-seed-round-to-accelerate-pocket-finding-platform [SID1234643158]). Existing investors are joined by YK Bioventures, bringing total funding to $26M. The additional raise will accelerate the company’s pipeline and expand their unique approach for finding new functional pockets on challenging targets.

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Ultimately, the biochemical properties of any small-molecule drug are constrained by its binding site, a pocket on its protein target. Despite advances in computational chemistry and structural biology, new functional pockets remain challenging to find. Think’s pocket-finding process programs microbes to build small molecules that bind to functional pockets, and they use these pockets to find hits in drug-like space. They have extended their platform technology to a striking variety of targets such as protein tyrosine phosphatases (PTPs), kinases (PTKs), proteases, and GTPases.

"Nature has endowed living systems with an extraordinary ability to build potent bioactive compounds, usually to fulfill important ecological functions, such as defense," said Dr. Jerome Fox, co-founder and CEO of Think Bioscience. "We are using a similar selection process to discover new functional pockets on challenging drug targets. New pockets are gold."

Gary Yeung, a managing partner at YK Bioventures, added, "We invested in Think Bioscience because of its transformational platform for new discoveries. Think Bio has already identified multiple novel pockets and generated strong pre-clinical data for its lead programs. We are eager to support Think Bio’s science-driven leadership team to advance these programs and to fund its growth."

Dr. Wendy Young will join the Board of Directors, which includes fellow veteran drug developer Nick Saccomano. Dr. Young has held leadership positions in biopharma for over 30 years and most recently spent 15 years at Genentech where she served as Senior Vice President of Small Molecule Drug Discovery and co-led research. She currently serves as a SAB member to Think, as well as several other biotech companies, and is an advisor at Google Ventures. "We look forward to working even more closely with Wendy," said Dr. Jerome Fox, co-founder and CEO at Think Bioscience. "Wendy and Nick bring a wealth of drug development expertise. Their guidance will be invaluable as we expand our platform to new classes of important targets and push pipeline programs toward the clinic."