On June 9, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing therapies that combine both targeted and immune-mediated mechanisms, reported that key takeaways from the TPST-1120 clinical program provided by Mark Yarchoan, M.D., associate professor of oncology at Johns Hopkins School of Medicine, at its June 5th investor event held in connection with the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Press release, Tempest Therapeutics, JUN 9, 2022, View Source [SID1234615808]). The company also revised its cash guidance. Dr. Yarchoan also presented the TPST-1120 Phase 1 results in an oral presentation at ASCO (Free ASCO Whitepaper) on Tuesday, June 7.

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Dr. Yarchoan reviewed and discussed TPST-1120 results both as a single agent and in combination with nivolumab in a webcast presentation that is available on the Tempest website at View Source His conclusions include:

The monotherapy arm consisted of one of the more challenging groups of tumors to treat in a Phase 1 trial, e.g., dominated by patients with late-line pancreatic and cholangiocarcinoma (CCA), where he considered stable disease a "win."
A number of patients in the monotherapy arm had meaningfully-prolonged stable disease, showing that TPST-1120 has activity as a monotherapy
Two patients with IDH1 mutated CCA, a mutation found in ~15-30% of intrahepatic CCA, had stable disease extending out to five and ten months, respectively, vs. less than three months for historical standard-of-care values, indicating that an IDH1 mutation is a potential biomarker for patient sensitivity to TPST-1120
In the combination arm, two patients with renal cell carcinoma (RCC) and one with metastatic CCA achieved partial response when treated with the higher doses of TPST-1120 in combination with pembrolizumab
Both RCC patients had progressed on prior anti-PD1 therapy, providing strong evidence that TPST-1120 overcomes resistance to anti-PD1 therapy
The patient with metastatic CCA had received multiple lines of prior systemic therapy and was PDL1-negative, mismatch repair proficient, and had a TMB of less than 10 mutations per megabase, supporting that TPST-1120 can reprogram the TME in immune-resistant type cancers
TPST-1120 Monotherapy Results

In the monotherapy portion of the trial, 19 evaluable patients with late-line treatment-refractory solid tumors, including pancreatic, cholangiocarcinoma, and colorectal cancers, were treated with oral twice-daily TPST-1120. The results showed that 53% (10/19) of patients experienced clinical benefit in the form of disease control, including tumor shrinkage in 21% of the patients. Two patients with late-line CCA, an aggressive tumor type and disease setting usually unresponsive to therapy, including IO therapies, achieved durable stable disease and one of the patients achieved durable tumor shrinkage.

TPST-1120 and Nivolumab Combination Therapy Results

In the combination therapy portion of the trial, 15 evaluable patients with heavily-pretreated renal cell carcinoma, hepatocellular carcinoma (HCC) and CCA were treated with oral twice-daily TPST-1120 and the anti-PD-1 therapy, nivolumab. All of the HCC and RCC patients had received an approved anti-PD-1 therapy in at least one prior line of therapy and discontinued that treatment due to disease progression. Promising objective responses (RECIST v1.1) were observed in two patients with late-line RCC who had previously progressed on anti-PD-1 therapy without an objective response (ORR 50%, n=2/4, in evaluable RCC patients). A third RECIST response was observed in a patient with late-line, heavily pre-treated CCA, a tumor type generally not responsive to anti-PD-1 alone.

Notably, all three responders were treated at the two highest doses of TPST-1120 (ORR 30%, 3/10).

Safety

TPST-1120 was well tolerated as both a monotherapy and in combination with nivolumab. The majority of the treatment-related adverse events were Grade 1 and 2, and included nausea, fatigue and diarrhea. No dose-limiting toxicities were reported during dose escalation.

Financial Update

Following the $15 million private investment in public equity financing completed in April 2022, Tempest’s cash and cash equivalents are currently expected to be sufficient to fund its current operating plans into the first quarter of 2024.

About TPST-1120

TPST-1120 is a first-in-class1 oral selective PPAR⍺ antagonist with a dual mechanism designed to target both tumor cells directly and suppressive immune cells in the tumor microenvironment. Both types of targeted cells are dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy and in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In addition to the study presented at ASCO (Free ASCO Whitepaper), in collaboration with F. Hoffmann La Roche, TPST-1120 is also advancing through a randomized, first-line, global, Phase 1b/2 clinical study in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic hepatocellular carcinoma.

On June 9, 2022 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat ESR1-mutated metastatic breast and gynecological cancers, reported that it will host a virtual update on its ELAINE Phase 2 clinical programs on Wednesday, June 15 at 10:00 a.m. EDT (Press release, Sermonix Pharmaceuticals, JUN 9, 2022, View Source [SID1234615825]).

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The event will feature presentations from Key Opinion Leaders (KOLs) Sarah Sammons, M.D. (Duke University) and Senthil Damodaran, M.D., Ph.D. (The University of Texas MD Anderson Cancer Center) who will discuss lasofoxifene, Sermonix’s investigational treatment for metastatic breast cancer with an acquired estrogen receptor 1 (ESR1) mutation.

Dr. Sammons will provide an overview of the ELAINE-1 study, an open-label, randomized, multicenter study evaluating the activity of lasofoxifene versus fulvestrant (the current standard of care) in patients who have progressed following treatment with an aromatase inhibitor (Al), including in combination with a CDK 4/6 inhibitor.
Dr. Damodaran will then provide an analysis of efficacy and safety data from the ELAINE-2 study, an open-label multicenter study evaluating lasofoxifene in combination with Lilly’s CDK 4/6 inhibitor abemaciclib (VERZENIO), which was provided by Eli Lilly and Co for the study.
Following Dr. Damodaran and Dr. Sammons’ presentations, the Sermonix leadership team will provide a company overview and update.

Interested participants are required to register in advance for the event and may do so here.

Key Opinion Leader Biographies

Sarah Sammons, M.D.

Sarah Sammons, M.D. is currently an assistant professor of medicine at Duke University/Duke Cancer Institute. Her clinical focus is in breast medical oncology and she has expertise in treating patients with all subtypes of metastatic breast cancer. She serves as assistant director of breast cancer clinical research at Duke Cancer Institute and as breast leader for the Centers of Brain Metastases and the Cancer Immunotherapy Research.

Her research focuses on the development of novel therapies for the treatment of metastatic breast cancer. She has designed and implemented several institutional, national and international clinical trials in advanced breast cancer. She also has a translational focus on understanding breast tumors that may respond to immunotherapeutic strategies and how to enhance them.

Senthil Damodaran, M.D., Ph.D.

Senthil Damodaran, M.D., Ph.D. is a medical oncologist/physician scientist with expertise in breast cancers, cancer genomics and development of novel targeted therapies. Dr. Damodaran serves as assistant professor in breast medical oncology with a joint appointment in investigational cancer therapeutics at MD Anderson Cancer Center.

He focuses on 1) genomics-driven clinical trials, 2) application of genomics for target discovery in breast cancers, and 3) characterization of secondary drug resistance mechanisms. At MD Anderson, he led their department’s genomic-directed clinical/translational efforts.

Dr. Damodaran is actively involved in several National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) initiatives. He serves as the chair for the NCI MATCH (Molecular Analysis for Therapy Choice) trial (Sub-protocol Z1F) and co-chair for upcoming ComboMATCH studies. He also serves as PI for genomically matched NCI-ETCTN study evaluating copanlisib in combination with trastuzumab and pertuzumab in HER2 +ve MBC with PIK3CA or PTEN alterations. Additionally, Dr. Damodaran serves as PI for the INTERACT study, which employs real-time ctDNA monitoring to identify secondary ESR1 alterations as well as genomically targeted study of futibatinib (TAS120) in MBC patients with FGFR amplifications. He also serves as the co-lead for post-mortem tissue collection protocol for metastatic breast cancer, a first of its kind at MD Anderson. In addition, he serves on the ABIM/ASCO Breast Question Writing group and the ASCO (Free ASCO Whitepaper) biomarker expert panel.

About Lasofoxifene

Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a potent, oral SERM could, if approved, play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer.

On June 9, 2022 Quanterix Corporation (NASDAQ: QTRX), a company digitizing biomarker analysis with the goal of advancing the science of precision health, reported that its Chief Executive Officer, Masoud Toloue, will join the Goldman Sachs 43rd Annual Global Healthcare Conference for a fireside chat on June 16, 2022 at 8:40 a.m., EST (Press release, Quanterix, JUN 9, 2022, View Source [SID1234615841]).

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To register for the live webcast, please visit: View Source

Toloue will also host one-on-one meetings with institutional investors on Thursday, June 16. A live webcast of the conversation will be available on the investor section of the Quanterix website at View Source Replays of the webcast will be available on the Quanterix website for 90 days following the conference.

On June 9, 2022 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved Tecentriq (atezolizumab) as an adjuvant treatment, following complete resection and platinum-based chemotherapy, for adults with non-small cell lung cancer (NSCLC) with a high risk of recurrence* whose tumours express PD-L1≥50% and who do not have EGFR mutant or ALK-positive NSCLC (Press release, Hoffmann-La Roche, JUN 9, 2022, View Source [SID1234616238]).

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"Today’s approval represents an important advance, as Tecentriq becomes the first cancer immunotherapy approved in Europe for the treatment of certain types of early-stage NSCLC," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Since approximately half of all people with early NSCLC develop recurrence after surgery, which in some cases is no longer curable, treating this cancer at an earlier stage offers the best chance to prevent recurrence."

This approval is based on results from an interim analysis of the Phase III IMpower010 study. The results showed treatment with Tecentriq, following complete resection and platinum-based chemotherapy, reduced the risk of disease recurrence or death (DFS) by 57% (hazard ratio [HR]=0.43, 95% CI: 0.26-0.71)** in people with resected Stage II-IIIA NSCLC (UICC/AJCC 7th edition) whose tumours express PD-L1≥50%, who do not have EGFR mutant or ALK-positive NSCLC, compared with best supportive care (BSC).1 A DFS benefit was consistently seen across most subgroups including histology or stage of disease with adjuvant Tecentriq, compared with BSC. Overall survival (OS) data for patients with PD-L1 high resected Stage II-III NSCLC, and who do not have EGFR mutant or ALK-positive disease are immature and were not formally tested at the DFS interim analysis, however, a trend towards OS improvement with Tecentriq was seen, with a stratified HR of 0.39 (95% CI: 0.18-0.82).2

Follow-up will continue with planned analyses of more mature OS data later this year. Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified.1

"Today’s approval now offers patients in Europe, whose tumours express high levels of PD-L1, the opportunity to reduce their risk of disease recurrence following surgery and chemotherapy," said Professor Enriqueta Felip, Head of the Thoracic Cancer Unit at Vall d’Hebron Institute of Oncology, Barcelona, Spain. "This milestone reinforces the need for biomarker testing at diagnosis for all people with NSCLC, irrespective of disease stage, to ensure they receive optimal treatment."

To date, Tecentriq has been approved in 19 countries, including the US and China, as adjuvant treatment, following complete resection and chemotherapy, for adults with Stage II-IIIA NSCLC (UICC/AJCC 7th edition) whose tumours express PD-L1≥1%. In three countries, including Canada and the UK, Tecentriq has been approved as adjuvant, treatment following complete resection and chemotherapy, for adult patients with Stage II-IIIA NSCLC (UICC/AJCC 7th edition) whose tumours have PD-L1 expression on ≥50% of tumour cells.

Tecentriq has shown clinically meaningful benefit in various types of lung cancer, with six currently approved indications in countries around the world. It was the first approved cancer immunotherapy for the first-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy). Tecentriq also has four approved indications in advanced or metastatic NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies. Tecentriq is available in three dosing options, providing the flexibility to choose administration every two, three or four weeks.

Roche has an extensive development programme for Tecentriq including multiple ongoing and planned Phase III studies across lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumour types.

About the IMpower010 study
IMpower010 is a Phase III, global, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC/AJCC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomised 1,005 people with a ratio of 1:1 to receive either Tecentriq (up to 16 cycles) or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomised Stage II-IIIA and intention-to-treat (ITT) Stage IB-IIIA populations. Key secondary endpoints include overall survival in the overall study population, ITT Stage IB-IIIA NSCLC.

About lung cancer
Lung cancer is one of the leading causes of cancer death globally.3 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.3 Lung cancer can be broadly divided into two major types: NSCLC and SCLC. NSCLC is the most prevalent type, accounting for around 85% of all cases.4 Approximately 50% of patients with NSCLC are diagnosed with early-stage (Stages I and II) or locally advanced (Stage III) disease.4 Today, about half of all people with early lung cancer still experience a cancer recurrence following surgery.5 Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.

About Tecentriq
Tecentriq is a cancer immunotherapy approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq was the first cancer immunotherapy approved for the treatment of a certain type of early-stage non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and hepatocellular carcinoma (HCC). Tecentriq is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer, PD-L1-positive metastatic triple-negative breast cancer and BRAF V600 mutation-positive advanced melanoma.

Tecentriq is a monoclonal antibody designed to bind with a protein called programmed death ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. In addition to intravenous infusion, the formulation of Tecentriq is also being investigated as a subcutaneous injection to help address the growing burden of cancer treatment for patients and healthcare systems.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have six approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with an innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

On June 9, 2022 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported data from a preclinical combination study of SON-1010 with a commercially available anti-PD1 compound (Press release, Sonnet BioTherapeutics, JUN 9, 2022, View Source [SID1234615826]). These results suggest that dosing of SON-1010 (IL12- FHAB) in combination with anti-PD1 demonstrated strong efficacy in the B16F10 mouse melanoma model, historically known as an immunologically insensitive model to anti-PD1.

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Checkpoint inhibitors provide viable treatment alternatives to chemotherapy and/or radiation for patients with solid tumors, but there remains a robust need for more effective combination treatment regimens. With the objective of improving the checkpoint inhibitor response rate, Sonnet BioTherapeutics is developing a targeted approach using the company’s Fully Human Albumin binding (FHAB) platform. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only Interleukin 12 (IL-12), but a variety of synergistic and potent immunomodulators. SON-1010 is currently undergoing Phase 1 clinical study in cancer patients and this preclinical study was designed to explore the combination potential with a checkpoint inhibitor (anti-PD1).

"We are excited to see that the combination of SON-1010 with an anti-PD1 antibody yielded compelling data in this preclinical model" said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer, and further added that, "These data support our strategy of pairing SON-1010 with a checkpoint inhibitor, with the goal of developing an improved treatment option for cancer patients."

Experimental Study Design: Three randomized cohorts of nine mice (n = 27), each with 150 mm3 B16F10 melanoma tumors, were dosed with 3µg IL12-FHAB and/or 10µg anti-PD1 antibody on days 0, 4 and 8 while the placebo cohort was not treated. Mean tumor volumes were measured every two or three days through an 18-day period.

Table 1: Mean Comparisons of Tumor Volume Growth Inhibition

Test Article

Mean Tumor
Volume (mm3) – Day 14

Tumor Growth Inhibition Ratios
( % Inhibition )

Placebo (n = 9)

2260

–

Anti-PD1 antibody (n = 9)

2016

10.7%

Anti-PD1 + IL12-FHAB (n = 9)

472

79.1%

Compared to the tumor-bearing placebo group at day 14, the treatment groups administered three doses of anti-PD1 antibody or three doses of the IL12-FHAB + anti-PD1 antibody combination resulted in 10.7% and 79.1% tumor growth inhibition, respectively.

Survival data for study mice at 18 days further supports the efficacy synergy of IL12-FHAB co-injected with anti-PD1 by improving the survival rate: (i) for anti-PD1 administration, only one mouse survived out of a total of nine, and (ii) for anti-PD1 + IL12-FHAB administration, seven mice survived out of a total of nine. Additionally, the mice cohorts used in the preclinical efficacy study did not show any weight loss during the study in either the single agent or combination dosing arms.

"We are excited to have demonstrated these important data in an immunologically distinct animal model when IL12-FHAB was dosed in combination with an anti-PD1 antibody," said John Cini, Ph.D., Sonnet’s Chief Scientific Officer. "Further, this study evaluated the sequence of test article administration, whereby co-injection of IL12-FHAB and anti-PD1 antibody was optimal when compared to administration of either anti-PD1 or IL12-FHAB first. Targeting the tumor by linking IL-12 to an albumin-binding domain extends the cytokine half-life in the body, and we believe that is the key to inducing a successful local immune response in the tumor microenvironment."