Agenus Selected for Late-Breaking Oral Presentation at ESMO-GI

On May 3, 2023 Agenus (Nasdaq: AGEN), a leading immuno-oncology company dedicated to developing innovative treatments for cancer and infectious diseases, reported a data update on botensilimab (multifunctional CTLA-4 antibody) in combination with balstilimab (PD-1 antibody) for patients with non-microsatellite instability-high metastatic colorectal cancer (non-MSI-H mCRC) has been selected for a late-breaking oral presentation at the upcoming ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer (ESMO GI), to be held June 28 – July 1, 2023 in Barcelona, Spain (Press release, Agenus, MAY 3, 2023, View Source [SID1234630945]).

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Presentation Details:

Abstract Title: Results from an expanded phase 1 trial of botensilimab, a multifunctional anti-CTLA-4, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (NCT03860272)
Abstract Number: LBA-4
Presenting Author: Andrea J. Bullock, MD, MPH, Assistant Professor of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center
Presentation Date and Time: 6/30/2023, 6:00pm – 6:10pm CEST

Data presented at the conference will be available to view in the Publications section of the Agenus website (View Source) following the ESMO (Free ESMO Whitepaper) GI Conference.

About Botensilimab
Botensilimab is a novel, multifunctional CTLA-4 investigational antibody that has been designed to extend clinical benefits to "cold" tumors that have not historically responded to standard of care or investigational therapies. In addition to binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and delivers better priming and activation of T cells, thereby amplifying immune responses.

In a Phase 1b clinical study of more than 350 patients, botensilimab has demonstrated clinical responses in nine, previously IO unresponsive, solid tumor cancers, either alone or in combination with Agenus’ PD-1 antibody, balstilimab (data presented at ASCO (Free ASCO Whitepaper) GI 2023, SGO 2023, CTOS 2022, SITC (Free SITC Whitepaper) 2022). Agenus is conducting global, randomized Phase 2 trials in non-MSI-H mCRC, melanoma, and pancreatic cancer as part of its ACTIVATE trial programs. Additional information about these botensilimab trials can be found at www.clinicaltrials.gov under the identifiers NCT05608044, NCT05630183, and NCT05529316, respectively. A global Phase 3 trial in non-MSI-H mCRC is expected to launch in 2023.

New Data Published In Cancer Suggest Decipher GRID-Derived Gene Expression Signature Could Enable More Personalized Treatment for Prostate Cancer Patients

On May 3, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that data published in the journal Cancer show the ability of a novel gene expression signature to classify prostate cancer into distinct molecular subtypes that may inform which tumors are more likely to respond to different treatments (Press release, Veracyte, MAY 3, 2023, View Source [SID1234630943]). The findings suggest that the novel biomarker, derived largely using Veracyte’s Decipher Genomics Resource for Intelligent Discovery (GRID) database, could potentially enable physicians to further personalize care for their patients with prostate cancer.

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"Prostate cancer is a heterogeneous disease with multiple, available therapeutic approaches in both its early and late stages, and insufficient tools to guide therapeutic selection and sequencing for individual patients," said Edward M. Schaeffer, MD, PhD, chair of Urology at Northwestern University, and senior author on the Cancer manuscript. "Our findings suggest that a molecular subtyping tool based on prostate cancer-specific biological processes could help guide treatment decisions and fuel precision medicine approaches for this disease."

Dr. Schaeffer and colleagues used 32,000 prostate cancer gene expression profiles from Veracyte’s Decipher GRID database to create a prostate subtyping classifier (PSC) model that identified four prostate cancer subtypes with distinct biological and clinical features: luminal differentiated, luminal proliferating, basal immune, and basal neuroendocrine-like. They then used data from 68,547 Decipher GRID profiles, along with those from five additional clinical cohorts, to evaluate the ability of the PSC to provide information about tumor aggressiveness and susceptibility to specific treatments.

The researchers identified many distinct differences within and between the four subtypes in terms of molecular features and pathways, including higher or lower frequency of gene loss and gene mutations that are known to contribute to tumor aggressiveness and/or treatment response. Additionally, the four subtypes demonstrated differences in clinicopathological features such as prostate specific antigen (PSA) values, frequency of non-organ confined disease, lower- or higher-grade disease, tumor aggressiveness, and time to metastasis following radical prostatectomy. Finally, the researchers report associations between individual subtypes and response to specific treatments, such as androgen deprivation therapy (ADT), radiotherapy, and docetaxel chemotherapy, as well as predicted responses to multiple novel systemic therapies.

"These findings reinforce the value of our Decipher GRID database for providing researchers with new insights that could advance understanding about the molecular origins and pathways specific to prostate cancer and their impact on patients’ response to treatment," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology.

The Decipher GRID database includes more than 100,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its research partners to help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis to physicians who have ordered the Decipher Prostate Genomic Classifier.

United Therapeutics Corporation Reports First Quarter 2023 Financial Results

On May 3, 2023 United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, reported its financial results for the quarter ended March 31, 2023 (Press release, United Therapeutics, MAY 3, 2023, View Source [SID1234630942]). Total revenues in the first quarter of 2023 grew 10% year-over-year to $506.9 million, compared to $461.9 million in the first quarter of 2022.

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"The hard work and determination of our over 1,000 Unitherians during the first quarter of this year allowed us to reach over $500 million in revenue for the second quarter ever," said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer. "And to sustain our mission to help patients in need, our clinical team continues to progress our four registration studies in progress: the two TETON studies of Tyvaso in idiopathic pulmonary fibrosis, the ADVANCE OUTCOMES study of ralinepag in pulmonary arterial hypertension, and the clinical study of our CLES ex vivo lung perfusion technology."

"We are extremely pleased with the underlying strength of our Tyvaso franchise, highlighted by record referrals and starts during the quarter and net patient additions in line with prior quarters," said Michael Benkowitz, President and Chief Operating Officer. "Our other core products also performed well, led by Orenitram which achieved record revenues in the first quarter."

First Quarter 2023 Financial Results

Key financial highlights include (dollars in millions, except per share data):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Total revenues

$

506.9

$

461.9

$

45.0

10

%

Net income

$

240.9

$

239.9

$

1.0

%

Net income, per basic share

$

5.20

$

5.31

$

(0.11)

(2

) %

Net income, per diluted share

$

4.86

$

5.03

$

(0.17)

(3

) %

Revenues

The table below presents the components of total revenues (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Net product sales:

Tyvaso(1)

$

238.4

$

172.0

$

66.4

39

%

Remodulin(2)

121.4

131.7

(10.3)

(8

) %

Orenitram

88.2

82.8

5.4

7

%

Unituxin

49.1

55.6

(6.5)

(12

) %

Adcirca

7.3

9.8

(2.5)

(26

) %

Other

2.5

10.0

(7.5)

(75

) %

Total revenues

$

506.9

$

461.9

$

45.0

10

%

(1)

Net product sales include both the drug product and the respective inhalation devices for both nebulized Tyvaso Inhalation Solution and the dry powder version known as Tyvaso DPI.

(2)

Net product sales include sales of infusion devices, such as the Remunity Pump.

Net product sales from our treprostinil-based products (Tyvaso, Remodulin, and Orenitram) grew by $61.5 million, or 16%, for the first quarter of 2023, as compared to the first quarter of 2022. The growth in Tyvaso revenues resulted primarily from an increase in quantities sold. The increase in quantities sold was driven by our launch of sales of Tyvaso DPI in June 2022 and continued growth in the number of patients following the Tyvaso label expansion in March 2021 to include the treatment of pulmonary hypertension associated with interstitial lung disease.

Expenses

Cost of sales. The table below summarizes cost of sales by major category (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Category:

Cost of sales

$

52.7

$

26.6

$

26.1

98

%

Share-based compensation benefit(1)

(0.4

)

(0.7

)

0.3

43

%

Total cost of sales

$

52.3

$

25.9

$

26.4

102

%

(1)

Refer to Share-based compensation below.

Cost of sales, excluding share-based compensation. Cost of sales for the three months ended March 31, 2023 increased as compared to the same period in 2022, primarily due to an increase in Tyvaso DPI royalty expense and product costs, following the commercial launch of the product in June 2022.

Research and development expense. The table below summarizes the nature of research and development expense by major expense category (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Category:

External research and development(1)

$

45.1

$

40.6

$

4.5

11

%

Internal research and development(2)

34.4

32.0

2.4

8

%

Share-based compensation expense (benefit)(3)

1.3

(3.6

)

4.9

136

%

Impairments(4)

%

Other(5)

2.1

2.1

NM(6)

Total research and development expense

$

82.9

$

69.0

$

13.9

20

%

(1)

External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product.

(2)

Internal research and development primarily includes salary-related expenses for research and development functions, internal costs to manufacture product candidates before FDA approval, and internal facilities-related expenses, including depreciation, related to research and development activities.

(3)

Refer to Share-based compensation below.

(4)

Impairments primarily includes impairment charges to write down the carrying value of in-process research and development and of certain property, plant, and equipment as a result of research and development activities. There were no impairment charges during the three months ended March 31, 2023 and March 31, 2022.

(5)

Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products and adjustments to the fair value of our contingent consideration obligations.

(6)

Calculation is not meaningful.

Research and development expense, excluding share-based compensation. Research and development expense for the three months ended March 31, 2023 increased as compared to the same period in 2022, primarily due to increased expenditures related to the TETON clinical studies of Tyvaso in patients with idiopathic pulmonary fibrosis.

Selling, general, and administrative expense. The table below summarizes selling, general, and administrative expense by major category (dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage Change

2023

2022

Category:

General and administrative

$

83.7

$

81.3

$

2.4

3

%

Sales and marketing

16.9

14.5

2.4

17

%

Share-based compensation benefit(1)

(13.3

)

(16.8

)

3.5

21

%

Total selling, general, and administrative expense

$

87.3

$

79.0

$

8.3

11

%

(1)

Refer to Share-based compensation below.

Share-based compensation. The table below summarizes share-based compensation benefit by major category

(dollars in millions):

Three Months Ended

March 31,

Dollar
Change

Percentage
Change

2023

2022

Category:

Stock options

$

4.9

$

5.5

$

(0.6

)

(11

) %

Restricted stock units

12.2

6.3

5.9

94

%

Share tracking awards plan (STAP)

(30.0

)

(33.4

)

3.4

10

%

Employee stock purchase plan

0.5

0.5

%

Total share-based compensation benefit

$

(12.4

)

$

(21.1

)

$

8.7

41

%

The decrease in share-based compensation benefit for the three months ended March 31, 2023, as compared to the same period in 2022, was primarily due to: (1) an increase in restricted stock unit expense driven by an increase in the number of awards granted and remaining outstanding for the three months ended March 31, 2023, as compared to the same period in 2022; and (2) a decrease in STAP benefit driven by a 19 percent decrease in our stock price and fewer awards remaining outstanding for the three months ended March 31, 2023, as compared to the same period in 2022.

Other (expense) income, net. The change in other (expense) income, net for the three months ended March 31, 2023, as compared to the same period in 2022, was primarily due to net unrealized gains and losses on equity securities.

Income tax expense. Income tax expense for the three months ended March 31, 2023 and 2022 was $51.0 million and $68.8 million, respectively. Our effective income tax rate (ETR) for the three months ended March 31, 2023 and 2022 was 17 percent and 22 percent, respectively. Our ETR for the three months ended March 31, 2023 decreased compared to our ETR for the three months ended March 31, 2022 primarily due to increased excess tax benefits from share-based compensation.

Webcast

We will host a webcast to discuss our first quarter 2023 financial results on Wednesday, May 3, 2023, at 9:00 a.m. Eastern Time. The webcast can be accessed live via our website at View Source A replay of the webcast will also be available at the same location on our website.

SpringWorks Therapeutics Reports First Quarter 2023 Financial Results and Recent Business Highlights

On May 3, 2023 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported first quarter financial results for the period ended March 31, 2023 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, MAY 3, 2023, View Source [SID1234630940]).

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"In the first quarter of 2023 we continued to deliver strong results across our diversified oncology pipeline. We were very pleased that our New Drug Application for nirogacestat in desmoid tumors was accepted with Priority Review by the FDA, and that our Phase 3 DeFi trial was published in the New England Journal of Medicine. Our team is energized by the opportunity to deliver the first FDA-approved therapy for this devastating disease and continues to work expeditiously to serve the desmoid tumor patient and physician communities following potential FDA approval later this year," said Saqib Islam, Chief Executive Officer of SpringWorks. "In parallel, we are advancing our Phase 2b ReNeu trial and believe that mirdametinib has the opportunity to address a substantial unmet need that remains for patients with NF1-associated plexiform neurofibromas. We are on track to report topline data from the trial later this year, with the goal of submitting an NDA in the first half of 2024. We look forward to sharing our continued progress throughout the year."

Recent Business Highlights and Upcoming Milestones

Rare Oncology

In February 2023, the U.S. Food and Drug Administration (FDA) accepted SpringWorks’ New Drug Application (NDA) for nirogacestat, an investigational oral, small molecule gamma secretase inhibitor, in development as a monotherapy for the treatment of adults with desmoid tumors. The application has been granted Priority Review and given a Prescription Drug User Fee Act (PDUFA) action date of August 27, 2023. SpringWorks also expects to file a Marketing Authorization Application for nirogacestat with the European Medicines Agency in 2024.
Data from the Phase 3 DeFi trial of nirogacestat in adult patients with progressing desmoid tumors were published in the March 9, 2023 edition of the New England Journal of Medicine.
SpringWorks expects to present topline data from the pediatric and adult cohorts of the Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in NF1-PN in the second half of 2023. Pending these data, SpringWorks anticipates submitting an NDA to the FDA for mirdametinib as a treatment for NF1-PN in the first half of 2024.
Patients continue to be enrolled in a Phase 2 trial evaluating nirogacestat in ovarian granulosa cell tumors.
B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma

SpringWorks continues to evaluate nirogacestat as part of several BCMA combination therapy regimens across treatment lines in collaboration with industry leaders. In 2023, SpringWorks expects that additional clinical data of nirogacestat in combination with BCMA-directed therapies will be presented and that additional planned Phase 1 collaborator studies will be initiated.
Biomarker-Defined Metastatic Solid Tumors

Updated clinical data from the Phase 1b trial evaluating mirdametinib in combination with BeiGene’s investigational RAF dimer inhibitor, lifirafenib, in patients with advanced or refractory solid tumors with RAS mutations, RAF mutations and other MAPK pathway aberrations were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2023. The combination showed antitumor activity in patients with various KRAS, NRAS, and BRAF mutations across several solid tumor types, including low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC), and endometrial cancer. These data support the advancement of this combination into the dose-expansion portion of the study, which will focus on a biomarker selected patient population with a tumor agnostic approach. The expansion is expected to start in the second half of 2023.
Updated clinical data from the Phase 1a/1b study of brimarafenib (BGB-3245), an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations were presented at AACR (Free AACR Whitepaper) in April 2023. Objective responders included patients with tumors harboring BRAF V600E that had progressed on prior BRAF/MEK inhibitors with or without checkpoint inhibitor treatment, BRAF Class II mutation, BRAF fusion, NRAS and KRAS mutations. These data supported the advancement of brimarafenib into the Phase 1b dose expansion portion of the study, which has been enrolling patients since October 2022 in defined cohorts.
Patients continue to be enrolled in the SpringWorks-sponsored Phase 1/2a combination study of brimarafenib and mirdametinib.
New preclinical data for SW-682, SpringWorks’ TEAD inhibitor, were presented at AACR (Free AACR Whitepaper) in April 2023. The data provide promising evidence of SW-682’s anti-tumor activity, a favorable pharmacokinetics profile and good tolerability in mice, and further support SpringWorks’ thesis that TEAD palmitoylation represents a rational point of intervention for Hippo-driven cancers. SpringWorks expects to file an Investigational New Drug Application for SW-682 in 2023.
General Corporate

SpringWorks continues to expand and strengthen its intellectual property portfolio. In March 2023, the United States Patent and Trademark Office issued U.S. Patent No. 11,612,588, which is directed to the treatment of desmoid tumors with pharmaceutical compositions of nirogacestat and expires in 2042. SpringWorks now has eight Orange Book-listable patents for nirogacestat.
First Quarter 2023 Financial Results

Research and Development (R&D) Expenses: R&D expenses were $33.5 million for the first quarter of 2023, compared to $34.1 million for the comparable period of 2022. The decrease in R&D expense was primarily attributable to a decrease in external costs related to drug manufacturing, clinical trial and other research, as well as facility-related costs, offset by an increase in internal costs driven by the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense.
General and Administrative (G&A) Expenses: G&A expenses were $44.2 million for the first quarter of 2023, compared to $27.4 million for the comparable period of 2022. The increase in G&A expense was largely attributable to commercial readiness activities to support the potential U.S. launch of nirogacestat for the treatment of adults with desmoid tumors. The increase in G&A included an increase in both internal costs and in consulting and professional services. The increase in internal costs was attributable to the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense, driven by the growth of our commercial organization, which included establishing certain sales, marketing, and commercialization functions. The increase in consulting and professional services was also primarily attributable to commercial readiness activities as we expand the capabilities of the organization.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $73.4 million, or $1.18 per share, for the first quarter of 2023. This compares to a net loss of $61.8 million, or $1.26 per share, for the comparable period of 2022.
Cash Position: Cash, cash equivalents and marketable securities were $528.1 million as of March 31, 2023.

Redx to Present Additional Preclinical Efficacy of RXC007 and DDR1/2 Inhibitors in Cancer-Associated-Fibrosis Models at The Resistant Tumour Microenvironment, Keystone Symposia

On May 3, 2023 Redx (AIM:REDX), the clinical-stage biotechnology company focused on discovering and developing novel, small molecule, highly targeted therapeutics for the treatment of cancer and fibrotic disease reported additional preclinical data from the company’s fibrosis portfolio including data on lead asset RXC007, and Discodin Domain Receptor (DDR) 1/2 inhibitors will be presented both orally and in a poster, at The Resistant Tumour Microenvironment, Keystone Symposia (7-10 May 2022, Vancouver, BC, Canada) (Press release, Redx Pharma, MAY 3, 2023, View Source [SID1234630939]).

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During the session on Wednesday 10 th May 0830-1130am PDT: ‘Friend or Foe: Should we Target Cancer Associated Fibroblasts and the ECM?’ Redx Senior Scientist, Dr. Daniel Wilcock will discuss if targeting tumor fibrosis with small molecule inhibitors of Rho Associated Coiled Coil Containing Protein Kinase 2 (ROCK2) or DDR1/2 improves therapy response in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC).

Data presented will be from the Company’s lead fibrosis asset, RXC007 as well as the DDR discovery programme, which further complements the data set presented last year at the Extracellular Matrix Pharmacology Congress by collaboration partner, the Garvan Institute of Medical Research. In addition to Dr Wilcock’s presentation, Redx will present a poster which details the potential of RXC007 in an aggressive patient derived xenograft model of PDAC in combination with standard of care (SoC) chemotherapy, and DDR1/2 inhibition in a TNBC model in combination with anti-PD-1.

RXC007, the Company’s lead asset, is a highly potent, selective and orally-active ROCK2 inhibitor targeting multiple diseases associated with fibrosis, initially being developed for interstitial lung diseases. A Phase 2a study assessing RXC007 as a potential treatment for patients with idiopathic pulmonary fibrosis (IPF) is expected to report topline data in Q1 2024.

Details of the presentation are as follows:

Title: Targeting tumor fibrosis with small molecule inhibitors of ROCK2 or DDR1/2 improves therapy response in preclinical models of PDAC &TNBC
Session: Friend or Foe: Should we Target Cancer Associated Fibroblasts and the ECM?

Day/Date: Wednesday 10 th May, 2023 Time: 08:30-11:30 am PDT

A copy of the poster will be made available on the Company’s website following the presentation at: View Source