On September 20, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX: 13) reported that it has initiated a Japan registration-enabling bridging study for surufatinib to support the registration of surufatinib in the treatment of patients with advanced neuroendocrine tumors ("NETs") (Press release, Hutchison China MediTech, SEP 20, 2021, View Source [SID1234587947]). The first patient was dosed on September 15, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Based on dialogue with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), it was agreed that the surufatinib Japanese new drug application ("NDA") for the treatment of advanced NETs include results from a pivotal study to be conducted in Japan, to complement the registration data package supporting the NDA to the U.S. Food and Drug Administration ("FDA") (accepted for review in June 2021) and the Marketing Authorization Application ("MAA") to the European Medicines Agency ("EMA") (validated in July 2021). The basis for the NDA and the MAA includes data from a U.S. Phase I/II study, as well as the completed Phase III SANET-ep and SANET-p studies used to support marketing authorization in China in advanced NETs, where surufatinib is currently marketed under the brand name SULANDA.

This Japan study is a two-stage, open label study of surufatinib where approximately 34 patients are expected to be recruited. In Part 1 of the study, the safety and tolerability of surufatinib 300mg once daily after 28 days of treatment will be assessed in patients with relapsed/refractory non-hematological malignancies; pharmacokinetics ("PK") and anti-tumor activity of surufatinib are secondary endpoints. In Part 2 of the study, efficacy will be assessed in patients with locally advanced or metastatic NETs; the primary outcome measure is objective response rate (ORR). The secondary outcome measures include disease control rate (DCR), progression free survival ("PFS"), duration of response (DoR), safety, and PK.

Surufatinib is the third potential new medicine discovered by HUTCHMED to enter into clinical development in Japan. A global Phase III registration study for fruquintinib, known as the FRESCO-2 study, is ongoing in patients with refractory metastatic colorectal cancer and is expected to enroll over 680 patients from over 150 sites in 14 countries, including Japan. A global single-arm, open-label study, known as the SAVANNAH study, is ongoing for savolitinib (partnered with AstraZeneca PLC) in combination with TAGRISSO in non-small cell lung cancer patients whose disease progressed following TAGRISSO due to MET amplification or overexpression.

About NETs

NETs form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. NETs are typically classified as pancreatic NET ("pNET") or extra-pancreatic (non-pancreatic) NET ("epNET").

According to Frost & Sullivan, there were 19,000 newly diagnosed cases of NET in the U.S. in 2020. Rates across the European Union (E.U.) appear largely similar to the U.S. This is supported by an analysis of global epidemiologic trends, which also show growth in the incidence of NETs worldwide.1 Importantly, NETs are associated with a relatively long duration of survival compared to other tumors. As a result, there were approximately 140,000 estimated patients living with NET in France, Germany, Italy, Spain, and the United Kingdom in 2020.2 In Japan, approximately 6,700 people were diagnosed with gastro-entero-pancreatic neuroendocrine neoplasms in 2016.3

About Surufatinib

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

HUTCHMED currently retains all rights to surufatinib worldwide.

About Surufatinib Development

epNETs in China: On December 29, 2020, surufatinib was granted drug registration approval by the National Medical Products Administration of China ("NMPA") for the treatment of epNET. Surufatinib is marketed in China under the brand name SULANDA. The approval was based on results from the SANET-ep study, a Phase III trial (clinicaltrials.gov identifier: NCT02588170) in patients with advanced epNETs conducted in China. The study met the pre-defined primary endpoint of PFS at a preplanned interim analysis, and was published in The Lancet Oncology4. Median PFS was significantly longer for patients treated with surufatinib at 9.2 months, compared to 3.8 months for patients in the placebo group (HR 0.334; 95% CI: 0.223-0.499; p<0.0001). Surufatinib had an acceptable safety profile, with the most common treatment related adverse events of grade 3 or worse being hypertension (36% of surufatinib patients vs. 13% of placebo patients), proteinuria (19% vs. 0%) and anemia (5% vs. 3%).

pNETs in China: On June 16, 2021, surufatinib was granted drug registration approval by the NMPA for the treatment of pNET. The approval was based on results from the SANET-p study, a Phase III trial (clinicaltrials.gov identifier: NCT02589821) in patients with advanced pNET in China. The pre-defined primary endpoint of PFS was met at a preplanned interim analysis and was published in The Lancet Oncology5, demonstrating that surufatinib reduces the risk of disease progression or death by 51% in patients, with a median PFS of 10.9 months compared to 3.7 months on placebo (HR 0.491; 95% CI: 0.391-0.755; p=0.0011). The safety profile of surufatinib was manageable and consistent with observations in prior studies.

Immunotherapy combinations: HUTCHMED entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317), TUOYI (toripalimab) and TYVYT (sintilimab), which are approved as monotherapies in China.

NETs in the U.S. and Europe: A FDA NDA submission was accepted in June 2021, followed by a MAA submission to the EMA validated in July 2021. The basis to support these filings includes the completed SANET-ep and SANET-p studies, along with existing data from surufatinib in U.S. epNET and pNET patients (clinicaltrials.gov identifier: NCT02549937). In the U.S., surufatinib was granted Fast Track Designations for development in pNET and epNET in April 2020, and Orphan Drug Designation for pNET in November 2019.

HUTCHMED has initiated an Expanded Access Protocol (EAP) in the U.S. to ensure patients with NET with limited therapeutic options have access to this treatment. Regulatory clearance of this protocol has been granted by the FDA and this program is open for site activation (clinicaltrials.gov identifier: NCT04814732).

On September 20, 2021 THERADIAG (ISIN: FR0004197747, Ticker: ALTER), a company specializing in in vitro diagnostics and Theranostics, reported its half-year results to June 30, 2021, as approved by the Board of Directors on September 16, 2021 (Press release, Theradiag, SEP 20, 2021, View Source [SID1234587946]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Bertrand de Castelnau, CEO of Theradiag, commented: "Over the last year we have been reaping the fruit of the efforts undertaken on controlling our operating costs and on our marketing strategy. Indeed, the effectiveness of our strategic refocus is demonstrated by the considerable improvement in all our financial indicators in the first half despite an economic and public health context that remains uncertain. On the basis of buoyant activity for our innovative solutions and a healthier cost structure, we are intending to accelerate Theradiag’s development by implementing a strategic plan that is in keeping with our growth ambitions on our target markets. Biotherapy monitoring is a vast global market, and the coming semesters look promising for Theradiag".

"The solid improvement in these results demonstrate the success of the Company’s structuring phase initiated some semesters ago. They also materialize the work of Theradiag’s teams, who I would like to congratulate. We now have to accelerate our growth on our markets of choice, and in particular on the Theranostics market", added Chairman of the Board Pierre Morgon.

Revenue up 12.5% despite an uncertain public health situation

Over the six months to June 30, 2021, Theradiag generated revenue of €5.5 million, compared with €4.9 million in the first half of 2020, despite an economic and public health context characterized by persistent difficulties accessing hospital treatment for patients undergoing immunotherapy in all countries.

Theranostics activity continued its growth, increasing by +14.7% in H1, notably driven by dynamic sales of the automated i-Track10. Marked by strong growth for a number of semesters now, for the first time Theranostics activity accounted for the majority of Theradiag’s revenue over the first 6 months of 2021.

Theranostics activity undertaken in the United States in partnership with HalioDX generated revenue of €0.5 million, in line with the Company’s development plan, and was thus up by 33.6%. In its export business, the Company has maintained a buoyant level of activity, with sales increasing by 27.4% to €1.3 million. Penalized by the maintaining of plans blancs emergency plans in hospitals, activity in France slowed slightly, slipping 5.2% compared with the first half of 2020.

IVD (In Vitro Diagnostics) activity generated growth of +10.4%, with revenue totaling €2.7 million over the six months to June 30, 2021.

Substantial improvement in financial indicators thanks to better control over operating costs and a refocusing of Theradiag’s strategy on its fundamentals

Following strong growth in the second half of 2020, the operating loss continued to shrink significantly, by 57.9%, in the first half of 2021. This improvement illustrates Theradiag’s ability to develop commercially while continuing to ensure strict operating cost management. At the same time, as in previous semesters, Theradiag intensified its investments in R&D and in its commercial development in the United States in order to strengthen its leadership position in biotherapy monitoring in France and abroad. Furthermore, the Company has expanded its Quality team to be in a position to comply with the requirements of the new European Union directive with regard to in vitro diagnostic medical devices (IVDR).

In a similar vein, the net result before recurring items improved by a buoyant 84.3% compared with the same period of 2020. It is now close to breakeven, representing -0.4% of revenue.

The overall net loss, including non-recurring items, improved by 59.8% to -€92 thousand at June 30, 2021 versus -€229 thousand at June 30, 2020.

Cash position and financial structure

At June 30, 2021, Theradiag had €1.4 million in net available cash, compared with €3.5 million at December 31, 2020. This difference is the result of cash lags, now resolved, totaling €0.5 million, while investments in R&D and international development are in line with Theradiag’s strategic plan.

To finance its growth strategy on the biotherapy monitoring market while maintaining a solid financial structure, Theradiag is not ruling out the possibility of raising additional funds depending on market conditions and the progress of its strategic plan.

Reminder of the main H1 2021 highlights

· January 2021: CE marking for the four new i-Tracker test kits: i-Tracker Vedolizumab, i-Tracker Anti-Vedolizumab, i-Tracker Ustekinumab and i-Tracker Anti-Ustekinumab, on originator and biosimilar molecules

· January 2021: Signing of a contract to supply quality control reagents to Orgentec, a specialist in in vitro diagnostics notably in the field of autoimmunity, infectious diseases and molecular biology

May 2021: Participation in Humabdiag, a large-scale research project undertaken with the University of Tours targeting the bioproduction of monoclonal antibodies dedicated in particular to Theradiag and the entire biotherapy market.

On September 12, 2021 NanOlogy Presented the Corporate Presentation (Press release, NanOlogy, SEP 12, 2021, View Source;utm_medium=rss&utm_campaign=aua21_results_trial_nmibc [SID1234590052]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On September 19 2021 Novartis reported a collaboration with SOLTI Innovative Cancer Research (SOLTI) on HARMONIA, an international, randomized, Phase III, multicenter, open-label study of Kisqali (ribociclib) versus Ibrance (palbociclib), both in combination with endocrine therapy, in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer with a HER2-enriched (HER2E) intrinsic subtype (Press release, Novartis, SEP 19, 2021, View Source [SID1234587942]). HARMONIA is the first prospective Phase III trial to enroll patients selected by RNA-based molecular subtyping of their tumors and the first to directly compare two CDK4/6 inhibitors in patients with HR+/HER2- advanced breast cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The strength and consistency of the Kisqali overall survival data across the MONALEESA program reinforce there are differences among CDK4/6 inhibitors, and that Kisqali stands apart in its ability to help patients achieve their goal of more quality time," said Susanne Schaffert, PhD, President, Novartis Oncology. "HARMONIA, a novel head-to-head trial, is a testament to our bold development approach and will provide evidence on the unique profile of Kisqali and its unmatched benefit for HR+/HER2- advanced breast cancer patients. We are grateful to be collaborating on this important study with leading academic research groups."

The primary endpoint of HARMONIA is progression free survival (PFS), and the study will evaluate if Kisqali positively alters tumor biology, enabling a better response to endocrine therapy compared to Ibrance.

"HARMONIA will significantly advance clinical and translational knowledge to optimize the diagnosis and treatment of patients with advanced breast cancer," said Aleix Prat, SOLTI President, Head of the Medical Oncology Department at Hospital Clínic of Barcelona, Head of the Translational Genomics Group and Targeted Therapies in Solid Tumors at IDIBAPS and Professor of Medicine at the University of Barcelona. "As an experienced academic research group in the field of oncology, we are proud to be pioneering this first-of-a-kind research on breast cancer at the RNA level to recognize the value of intrinsic subtypes, which impact patient outcomes in terms of incidence, survival and response to treatment."

HARMONIA enrollment is expected to begin in Q1 2022. Patients with the basal-like subtype may also enroll. This exploratory cohort of patients will be treated with a chemotherapy-based regimen as these tumors behave more like triple-negative breast cancer.

About Kisqali (ribociclib)
Kisqali is the CDK4/6 inhibitor with the largest body of clinical trial evidence demonstrating consistent and superior overall survival benefit compared to endocrine therapy alone. Overall survival results were presented previously: MONALEESA-7 (ASCO 2019) and MONALEESA-3 (ESMO 2019) and MONALEESA-2 (ESMO 2021); MONALEESA-7 and MONALEESA-3 were published in the New England Journal of Medicine, with updated exploratory analyses presented at SABCS 2020 and ASCO (Free ASCO Whitepaper) 2021, demonstrating Kisqali plus endocrine therapy significantly extends life in pre/perimenopausal or postmenopausal women with HR+/HER2- advanced breast cancer2-4, 10-11.

Kisqali is approved by the US Food and Drug Administration (FDA) and by the European Commission (EC) as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor. Kisqali in combination with an aromatase inhibitor is approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine-based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA and by the EC12. Kisqali is approved in over 95 countries1.

Novartis is continuing to reimagine cancer with an additional trial of Kisqali. NATALEE is a large confirmatory clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)13.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Important Safety Information from the Kisqali EU SmPC
Kisqali (ribociclib) is a prescription medicine approved in combination with an aromatase inhibitor as initial endocrine – based therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer or fulvestrant as initial endocrine – based therapy or following disease progression on endocrine therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if Kisqali is safe and effective in children or adolescents. Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Kisqali is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali can harm an unborn baby. Females who are able to become pregnant and who take Kisqali should use highly effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid grapefruit or grapefruit juice while taking Kisqali. The most common side effects (incidence >=20%) include infections, white blood cell count decreases, headache, cough, nausea, tiredness, diarrhea, vomiting, constipation, hair loss and rash. The most common Grade 3/4 side effects (incidence >5%) were infections, low neutrophils, low leukocytes, low red blood cells, abnormal liver function tests, low lymphocytes, low phosphate levels and vomiting. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

On September 19, 2021 Byondis B.V., an independent, clinical stage biopharmaceutical company creating precision medicines, reported positive results from its pivotal Phase III TULIP study (Press release, Byondis, SEP 19, 2021, View Source;trastuzumab-duocarmazine-syd985-superior-to-physicians-choice-in-pre-treated-locally-advanced-or-metastatic-her2-positive-breast-cancer-301379760.html [SID1234587938]). The multi-center, open-label, randomized clinical trial compared the efficacy and safety of the company’s antibody-drug conjugate (ADC) [vic-]trastuzumab duocarmazine (SYD985) to physician’s choice (PC) treatment in patients with pretreated HER2-positive unresectable locally advanced or metastatic breast cancer (MBC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"SYD985 vs. Physician’s Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer" met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement over PC – 7 months for SYD985 versus 4.9 months for PC. The study also demonstrated a trend towards better overall survival (OS) for patients treated with SYD985. TULIP results were presented by Cristina Saura, M.D., head, Vall d’Hebron University Hospital Breast Cancer Unit, Medical Oncology Department, and principal investigator, Vall d’Hebron Institute of Oncology Breast Cancer Research Group in Barcelona, Spain.

"We are satisfied with the results of the TULIP study, as it bodes well for the potential of SYD985 as a new treatment option for patients with HER2-positive metastatic breast cancer, a disease typically associated with a poor prognosis," said Dr. Saura.

"The TULIP results represent a significant milestone in our R&D efforts, and we hope to make this next generation ADC available as soon as possible to the patients whose lives we are dedicated to improve," said Byondis CEO Marco Timmers, Ph.D. "We want to thank our clinical trial sites and study participants and their families for their contributions to this important research."

Byondis is working to complete the SYD985 biological license application (BLA) and intends to submit it to the U.S. Food & Drug Administration (FDA) before the end of 2021. The company is exploring partnerships with pharma and biopharma companies in order to further develop and commercialize SYD985.

The therapy was granted fast track designation by the FDA in January 2018. The designation was based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial (SYD985.001).[i]

More TULIP (SYD985.002) Results

Starting in November 2017, TULIP enrolled 437 female patients with a median age of 56 and a median of 4 prior MBC treatments. The study was conducted at 83 sites in 11 countries across the United States, Canada, Europe and Singapore. To qualify, patients had either: (1) progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease; or (2) progression during or after ado-trastuzumab emtansine treatment. Patients were randomly assigned (2:1) to receive SYD985 (n=291, 1.2 mg/kg q three weeks) or PC chemotherapy (n=146) until disease progression or unacceptable toxicity. The trial was powered to detect a Hazard Ratio (HR) of 0.65 at the P < 0.05 significance level.

The study’s primary endpoint, blinded centrally reviewed median PFS, was 7.0 months (5.4-7.2, 95% CI) for SYD985 and 4.9 months (4.0-5.5) for PC (HR 0.64 [0.49-0.84], p = 0.002). Secondary endpoint results are as follows: investigator-assessed PFS significantly improved, 6.9 months (6.0-7.2) versus 4.6 months (4.0-5.6) for PC (HR 0.60 [0.47-0.77], p < 0.001); OS first analysis indicated HR was 0.83 (0.62-1.09, p = 0.153); and no significant differences were observed in objective response rate (ORR) or health-related quality of life (HRQoL).

The most frequently reported adverse events (AEs) for SYD985 were conjunctivitis (38.2%), keratitis (38.2%) and fatigue (33.3%). For PC, the most frequently reported AEs were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease/pneumonitis was reported for 7.6% of patients treated with SYD985. AEs leading to discontinuation of treatment were 35.4% and 10.2% in the SYD985 and PC groups, respectively. In the SYD985 group, these were mainly related to eye disorders (20.8%) or respiratory disorders (6.3%).

[Vic-]Trastuzumab Duocarmazine (SYD985), a Next Generation Antibody-Drug Conjugate

[Vic-]trastuzumab duocarmazine (SYD985) incorporates Byondis’ distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine. Although in general, marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still need for improvement.

The ADC [vic-]trastuzumab duocarmazine is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of [vic-]trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 is considered a form of targeted chemotherapy.

[Vic-]trastuzumab duocarmazine is currently being investigated in three other studies. Byondis initiated a Phase II clinical trial in HER2-expressing recurrent, advanced or metastatic endometrial cancer, and a Phase I study exploring the synergistic effects of [vic-]trastuzumab duocarmazine and niraparib in patients with HER2-expressing locally advanced or metastatic solid tumors. [Vic-]trastuzumab duocarmazine is also part of a new arm of the Quantum Leap Health Collaborative I-SPY 2 TRIAL investigating the neoadjuvant use of [vic-]trastuzumab duocarmazine in HER2-low early-stage breast cancer.

ByonZine, Byondis’ Distinctive, Proprietary Linker-Drug Technology

While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, leading to premature release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis’ next generation ADCs are highly stable in circulation and carry an intricate, inactivated and potent cytotoxic drug that rapidly self-destructs if prematurely released, limiting damage to healthy tissue and improving the therapeutic window.

Byondis’ differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.

The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.

HER2-Positive MBC: A Cancer With a Poor Prognosis

Breast cancer was the world’s most common cancer in 2020,[ii] with an estimated 2.3 million new cases.[iii] Its incidence is rising, particularly in developing countries, where the majority of cases are diagnosed in late stages.[iv] Breast cancer is the leading cause of cancer death for women in more than 100 countries.[v]

In metastatic or Stage 4 breast cancer, the cancer spreads to other parts of the body, such as the lungs, liver, bones or brain. Approximately 0.5 million people worldwide die from MBC every year.[vi]

In HER2-positive breast cancer, an overexpression of the human epidermal growth factor receptor 2 (HER2) protein causes out-of-control reproduction of breast cells. Research has shown that women with HER2-positive breast cancer have a more aggressive disease, greater likelihood of recurrence and poorer prognosis, compared to women with HER2-negative breast cancer. About 20 percent of all breast cancers are HER2-positive, with younger women being the most affected. Treatment of HER2-positive breast cancer can consist of the following: surgery, radiation, chemotherapy and targeted treatments.[vii]