On September 5, 2024 Affimed, a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported financial results and provided an update on clinical and corporate progress for the quarter ended June 30, 2024 (Press release, Affimed, SEP 5, 2024, View Source [SID1234646694]).

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"We continue to generate compelling data across our clinical programs," said Dr. Andreas Harstrick, Chief Medical Officer of Affimed. "In solid tumors, our combination study is making significant progress, and we are excited to see objective responses and meaningful tumor control, even in patients with EGFR mutant lung cancer — a disease often resistant to immunomodulation. It’s particularly encouraging that these outcomes are achieved without chemotherapy, which is important given the intolerance many pretreated patients have for such treatments. Our programs in hematologic malignancies are also advancing well. Recent updates from the 12 patients of the LuminICE-203 study reveal remarkable efficacy, in an advanced Hodgkin lymphoma population that had exhausted all approved treatment options. Additionally, AFM28 continues to show promise as a monotherapy in AML. The data shared today underscore our strategy of leveraging the innate immune system in our fight against cancer and reinforce our commitment to advancing these clinical programs."

Pipeline Highlights:

AFM24 (EGFR / CD16A)
In the AFM24-102 trial (combination with atezolizumab):

24 heavily pretreated EGFRmut NSCLC patients are in the trial; in 17 patients that are response evaluable per protocol, 1 CR, 3 PRs and 8 SDs were observed. All responses have been confirmed by follow-up scan. ORR is 23.5% (4/17) and DCR is 70.6% (12/17). Median follow-up is > 7 months and 8 out of the 17 patients continue on treatment. All 4 responders remained on treatment for at least 7 months. Final PFS data from the EGFRmut cohort is expected at a scientific conference in H1 2025.
All patients were pretreated with TKIs (~60% with third generation TKIs) and the majority (76%) had also received platinum-based chemotherapy.
The EGFRwt NSCLC cohort of patients who failed chemotherapy and PD-1/PD-L1 has continued enrollment, with 40 patients on trial. ORR and safety for this cohort is expected in Q4 2024.
In May, the Company received FDA Fast Track designation for the combination treatment of AFM24 with atezolizumab for EGFRwt NSCLC patients.
Acimtamig (AFM13; CD30 / CD16A)
High efficacy observed in the first 12 patients with advanced HL in cohorts 1 and 2 of the Phase 2 LuminICE-203 study showing an ORR of 83.3 % and CRR of 50%.

In the multi-center, multi-cohort, open-label Phase 2 LuminICE-203 trial, patients with advanced, treatment refractory Hodgkin Lymphoma receive combination of CD30-targeting innate cell engager acimtamig (AFM13) with AlloNK.
All HL patients were heavily pretreated with a median of 4 lines of prior therapy, having exhausted all standard of care treatment options, including combination chemotherapy, brentuximab vedotin and checkpoint inhibitors; 50% of patients had also failed prior autologous or allogeneic stem cell transplantation (SCT).
Enrollment in cohorts 1 and 2 (acimtamig doses of 200 mg or 300 mg; AlloNK 2×109 per week for 3 weeks) is completed: In the 12 patients, 6 CRs and 4 PRs were observed.
Enrollment in cohorts 3 and 4 (acimtamig 200 mg or 300 mg; 4×109 in week one and 2×109 AlloNK in weeks 2 and 3) has progressed well with 10/12 patients on study.
Treatment related adverse events were consistent with previous experience and side effects related to acimtamig and AlloNK were well manageable with standard of care treatment.
Data from the study is expected to be presented at a scientific conference in Q4 2024.
AFM28 (CD123 / CD16A)
In the sixth cohort (300 mg) of the multi-center Phase 1 open-label, dose-escalation study (AFM28-101), of AFM28 monotherapy in CD123-positive r/r AML, 3 out of 6 patients (50%) showed a CR or CRi.

Of 6 patients treated at dose level 6 at 300 mg, 1 patient showed a CR, 2 patients a CRi for a composite complete response rate (CRcR, defined as CR+CRi) of 50% (3/6) and 2 patients achieved SD.
Of 6 patients treated at dose level 5 at 250 mg, 1 patient showed a CR, lasting 6 months, a CRR of 17% (1/6) ; the other 5 patients achieved SD as best response.
No dose-limiting toxicities were reported in dose levels 5 and 6.
An additional 6 patients will be enrolled at 300 mg of AFM28.
Data from the study is expected to be presented at a scientific conference in Q4 2024.
Upcoming Milestones:

LuminICE-203: Efficacy update of cohorts 1-4 expected to be presented at a future scientific conference in Q4 2024.
AFM24-102: ORR and safety data from the EGFRwt cohort in Q4 2024.
AFM28-101: Data from the study is expected to be presented at a scientific conference in Q4 2024.
AMF24-102: Mature PFS data from EGFRmut and EGFRwt cohorts expected to be presented at a future conference in H1 2025.
Second Quarter 2024 Financial Highlights
Affimed’s consolidated financial statements are prepared in accordance with International Financial Reporting Standards (IFRS) as issued by the International Accounting Standard Board (IASB). The consolidated financial statements are presented in Euros (€), the Company’s functional and presentation currency.

As of June 30, 2024, cash, cash equivalents and short-term investments totaled €34.4 million. Based on current operating and budget assumptions, the Company expects that cash, cash equivalents and investments, together with anticipated proceeds from its ATM program and the sale of AbCheck, will finance its operations into the second half of 2025.

Net cash used in operating activities for the quarter ended June 30, 2024 was €16.5 million compared to €33.2 million for the quarter ended June 30, 2023. The decline was mainly due to lower research and development expenditure and personnel expenses due to the reduction in head count.

Total revenue for the quarter ended June 30, 2024, was €0.2 million compared with €1.4 million for the quarter ended June 30, 2023. Revenue in 2024 only related to a platform license provided to Genentech and 2023 predominantly related to the Roivant research collaborations for which all work has been completed.

Research and development expenses for the quarter ended June 30, 2024, were €11.7 million compared to €25.3 million in 2023. The decrease was primarily a result of lower expenses associated with the development of acimtamig and AFM24, due to a decrease in procurement of clinical trial material, clinical trial costs and manufacturing costs, decrease in head count due to the corporate restructuring.

General and administrative expenses for the quarter ended June 30, 2024, were €4.0 million compared to €6.3 million for the quarter ended June 30, 2023. The decrease was due to declines in headcount, in legal and consulting expenses, insurance expenses and share-based payment expenses.

Net loss for the quarter ended June 30, 2024, was €15.5 million, or €1.01 loss per common share compared with a net loss of €29.4 million, or €1.97 loss per common share, for the quarter ended June 30, 2023.

The weighted number of common shares outstanding for the quarter ended June 30, 2024, was 15,300,912 shares.

Additional information regarding these results will be included in the notes to the consolidated financial statements as of June 30, 2024, included in Affimed’s filings with the U.S. Securities and Exchange Commission (SEC).

Note on International Financial Reporting Standards (IFRS)
Affimed prepares and reports consolidated financial statements and financial information in accordance with IFRS as issued by the IASB. None of the financial statements were prepared in accordance with U.S. Generally Accepted Accounting Principles. Affimed maintains its books and records in Euro.

Conference Call and Webcast Information
Affimed will host a conference call and webcast on September 5, 2024, at 8:30 a.m. EDT / 14:30 CET to discuss second quarter 2024 financial results and corporate developments.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link: https://register.vevent.com/register/BI53034c7725d043b0854377307e1cd8a3, and you will be provided with dial-in details and a pin number.

Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call.

On September 5, 2024 Nurix therapeutics presented its corporate presentation (Presentation, Nurix Therapeutics, SEP 5, 2024, View Source [SID1234646374]).

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On September 5, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) reported that it will present new data from the company’s broad lung cancer clinical development program during the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, taking place Sept. 7-10, 2024 in San Diego, Calif (Press release, Gilead Sciences, SEP 5, 2024, View Source [SID1234646390]). Data to be highlighted across three oral presentations include: initial results from two cohorts of the EVOKE-02 study of Trodelvy (sacituzumab govitecan-hziy) in previously untreated advanced or metastatic non-small cell lung cancer (mNSCLC), results from a subgroup analysis of the EVOKE-01 study of Trodelvy in second-line mNSCLC, and updated data from the TROPiCS-03 study of Trodelvy in extensive stage small cell lung cancer (ES-SCLC).

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New Findings Further Support the Potential Efficacy of Trodelvy for mNSCLC in the First-Line Setting

Results to be presented from Cohorts C (non-squamous) and D (squamous) of the Phase 2 EVOKE-02 study of Trodelvy in previously untreated mNSCLC in combination with pembrolizumab and carboplatin demonstrate encouraging efficacy in patients with non-AGA-driven mNSCLC and across PD-L1 status. These additional findings advance our scientific understanding of the optimal treatment regimens and appropriate patient populations with mNSCLC that may potentially benefit from treatment with Trodelvy in the first-line setting.

"Our data at WCLC will add to the expanding evidence for the potential of Trodelvy in lung cancer and reinforce our confidence in our broader lung cancer strategy," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "The totality of mature EVOKE-02 data suggest that in the first-line setting, Trodelvy in combination with pembrolizumab may have a greater potential to positively impact patients with mNSCLC when given without the addition of chemotherapy. These findings support the ongoing Phase 3 EVOKE-03 study and underscore our commitment to improving the standard of care for patients with lung cancer."

Analysis Shows Overall Survival (OS) Improvement with Trodelvy in a Subgroup of Second-Line mNSCLC Patients

Additionally, Gilead will present data from the EVOKE-01 study in the subgroup of patients whose tumors did not respond to their last anti-PD-(L)1-therapy, building on the primary analysis presented earlier this year. Results from a pre-specified analysis showed a numerical OS improvement vs. docetaxel in this patient population, which was observed across histologies and regardless of whether patients were stable or progressed after their last anti-PD-(L)1-containing treatment. This subgroup analysis was not alpha-controlled for formal statistical testing. These meaningful data in mNSCLC help advance our understanding of Trodelvy’s potential for patients with lung cancer.

Longer-Term Follow-up Data from the Phase 2 TROPiCS-03 ES-SCLC Cohort Demonstrate Promising Activity

Gilead will also share updated results from the global Phase 2 TROPiCS-03 ES-SCLC Cohort. These new data, with additional patients and longer-term follow-up, reinforce promising activity shown with Trodelvy treatment in patients with both platinum-resistant and platinum-sensitive disease and support further investigation of Trodelvy in ES-SCLC, where there is still significant unmet need.

Summary of Presentations

Accepted abstracts at WCLC 2024 include:

Date/Time

Abstract

September 8, 2:00 PM – 3:15 PM PT (Oral Presentation)

Abstract #OA04.04: Sacituzumab Govitecan as Second-Line Treatment in Patients with Extensive Stage Small Cell Lung Cancer

September 9, 10:45 AM – 12:00 PM PT (Oral Presentation)

Abstract #OA08.07: Sacituzumab Govitecan + Pembrolizumab + Carboplatin in 1L Metastatic Non-Small Cell Lung Cancer: The EVOKE-02 Study

September 9, 10:45 AM – 12:00 PM PT (Oral Presentation)

Abstract #OA08.06: Sacituzumab Govitecan vs. Docetaxel in Patients With mNSCLC non-Responsive to Last anti-PD-(L)1–Containing Regimen: EVOKE-01

Trodelvy has not been approved by any regulatory agency for the treatment of mNSCLC or ES-SCLC. Its safety and efficacy have not been established for this use. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for the approved U.S. Indications and Important Safety Information.

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast, bladder and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Trodelvy is also approved to treat certain patients with pre-treated HR+/HER2- metastatic breast cancer in Australia, Brazil, Canada, the European Union, Israel, United Arab Emirates and the United States. In the U.S., Trodelvy has an accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer; see below for full indication statements.

Trodelvy is being explored for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including mNSCLC, head and neck cancer, gynecological cancer, and gastrointestinal cancers.

U.S. Indications for Trodelvy

In the United States, Trodelvy is indicated for the treatment of adult patients with:

Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
U.S. Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI.

Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

Please see full Prescribing Information, including BOXED WARNING.

On September 5, 2024 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported the latest data from its eIF4E program will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain, September 13-17 (Press release, Ribometrix, SEP 5, 2024, View Source [SID1234646375]). A poster presentation will review in vitro and in vivo studies of a small molecule eIF4E inhibitor, RBX-6610, as a potential treatment for non-small cell lung cancer (NSCLC), specifically NSCLC with KRASG12C, a common mutation. Acquired resistance is observed in the majority of patients treated with the two approved therapies for KRASG12C mutant NSCLC, creating a significant opportunity for a therapy that resensitizes tumors to these treatments. Ribometrix’s data supports RBX-6610’s ability to deliver this mechanism in combination with the approved therapies. "The close relationship of eIF4E and KRAS signaling suggested the potential for eIF4E inhibition to restore tumor sensitivity to KRAS inhibition, and it is exciting to see this thesis borne out given the important medical need among patients with NSCLC," said Jessica Sorrentino, Ph.D., SVP of Translational Medicine. "We look forward to sharing our full dataset at ESMO (Free ESMO Whitepaper) 2024."

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In vitro outcomes in the poster include:

1. RBX-6610 monotherapy demonstrated consistent anti-proliferative effects in KRASG12C mutant tumor cell lines, in both treatment-naïve lines and those with acquired resistance

2. RBX-6610 combined with KRAS inhibitors resulted in a synergistic apoptotic induction in treatment-naïve tumor cells and re-sensitized resistant tumor cells to KRAS inhibitors.

In vivo outcomes in the poster include:

1. RBX-6610 monotherapy caused significant tumor growth inhibition

2. RBX-6610 combined with a KRAS inhibitor resulted in significant tumor regression in a treatment-naïve model

3. A further in vivo study reviewing RBX-6610’s ability to re-sensitize tumor cells to KRAS inhibition will be included in the final poster presentation.

The presentation details are:

Date: Sunday, September 15, 2024

Location: Dedicated poster area of Hall 6.

Presentation number: 202P

Title: eIF4E inhibition exhibits anti-tumor activity and re-sensitizes acquired resistant KRASG12C NSCLC to KRAS inhibitors

The ESMO (Free ESMO Whitepaper) poster will be available to view on the "Publications" page of Ribometrix’s website following the presentation.

About eIF4E

Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation and well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Based on substantial external and in-house data, Ribometrix is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors.

On September 5, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported the publication of a new study in Future Oncology further substantiating use of its DecisionDx-SCC test in guiding patient selection and decision-making related to the use of ART in patients with high-risk SCC based on the ability of the test to identify patients likely to benefit from treatment (Press release, Castle Biosciences, SEP 5, 2024, View Source [SID1234646391]).

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"Some patients with high-risk SCC are eligible for adjuvant radiation therapy once their primary tumor has been removed; however, determining which patients should seek treatment is complicated and involves weighing numerous pros and cons against the risk of the patient’s cancer returning," said Emily S. Ruiz, M.D., MPH, FAAD, lead author, board-certified dermatologist and Mohs micrographic surgeon at Brigham and Women’s Hospital in Boston, and Associate Professor of Dermatology at Harvard Medical School. "In this study, we were successful in validating, in an independent SCC patient cohort, that DecisionDx-SCC can objectively inform these challenging decisions by identifying patients for whom ART would be beneficial, as well as those who may be best served by avoiding it."

In the study, a novel, independent cohort of patients with high-risk SCC tumors (399 patients; 423 tumors) from two academic centers were tested using DecisionDx-SCC and analyzed for five-year metastasis-free survival and projected time to metastasis. Similar to the recent 2024 study by Arron et al., samples were controlled for bias by clinicopathologically matching ART-treated and untreated patients.1

A comparison of both studies (Arron et al. and Ruiz et al.) demonstrates very similar results:

Both studies showed that patients with DecisionDx-SCC Class 2B (highest metastatic risk) test results who were treated with ART had a 50% decrease in metastatic disease progression, on average, and a significant deceleration of disease progression compared to patients who did not receive ART.
Both studies reported no difference in disease progression rates when comparing ART-treated and untreated patients with DecisionDx-SCC Class 1 (lowest metastatic risk) test results, suggesting these patients may consider deferring treatment due to low metastatic risk and a low likelihood of benefitting from treatment. The majority of patients had Class 1 results, confirming the significance of clinical utility in ruling out ART in these patients.
Additionally, both studies observed a lack of ART-related benefit for patients with Class 2A (higher metastatic risk) test results, despite having an intermediate-level risk of metastasis compared to patients with Class 1 and Class 2B test results. This suggests that a specific pattern of gene expression captured uniquely by a DecisionDx-SCC Class 2B result may be driving the identification of the benefit from ART.
"This marks the sixth study since the start of 2024 demonstrating the value of DecisionDx-SCC test results in improving risk-aligned patient care through precise, tumor-biology-based risk stratification," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "The more than 20 peer-reviewed papers published since the launch of our test four years ago speaks to the breadth of evidence supporting the test’s validity, as well as its ability to improve upon clinicopathologic-based staging systems to drive optimized decision-making regarding appropriate treatment pathways for patients with high-risk SCC."

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to stratify risk of metastasis in patients with cutaneous squamous cell carcinoma who have one or more NCCN high-risk factors. The test result, in which patients are stratified into a Class 1 (low), Class 2A (higher) or Class 2B (highest) risk category, predicts individual metastatic risk to inform risk-appropriate management and guide decision-making regarding the use of adjuvant radiation therapy. Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that the test can significantly improve risk-stratification when used with traditional staging systems and clinicopathologic risk factors to guide risk-aligned management and treatment decisions. Learn more at www.CastleBiosciences.com.