On October 13, 2020 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small molecule oncology therapeutics, reported that it has dosed the first patient in its phase 1/2 adaptive-design clinical trial of its lead-product-candidate, LNS8801, in combination with KEYTRUDA (pembrolizumab) in patients who had previous clinical benefit from immune checkpoint inhibitors and then subsequently progressed (Press release, Linnaeus Therapeutics, OCT 13, 2020, View Source [SID1234568436]). This marks the first time any company has dosed a patient in a clinical trial specifically targeting the G protein-coupled estrogen receptor (GPER) in combination with pembrolizumab. The initiation of the study follows the successful identification of the recommended phase 2 dose (RP2D) in the Company’s ongoing study of LNS8801.

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LNS8801 is an orally bioavailable small molecule that is a highly specific and potent agonist of the GPER. LNS8801 is currently finishing the dose escalation portion of its phase 1/2 study assessing the safety, tolerability, pharmacokinetics and preliminary efficacy in patients with advanced cancer.

"We are extremely pleased to begin testing LNS8801 in combination with pembrolizumab in this patient population. In our phase 1 trial of LNS8801 we have seen biological and clinical signals that suggest LNS8801 in combination with pembrolizumab may have activity based on the preclinical rationale and reverse resistance to immune checkpoint inhibitors. We currently have six outstanding academic comprehensive cancer centers all enthusiastically recruiting patients for this promising study," commented Patrick Mooney, MD, chief executive officer of Linnaeus. "We believe that LNS8801 with pembrolizumab has potential to provide meaningful clinical benefit for patients with cancer, and we look forward to providing updates over the course of the study."

The study entitled, "A Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of LNS8801 in Patients with Advanced Cancer Including Immunotherapy Refractory Expansion Cohorts with and without Pembrolizumab," was designed in two parts. The phase 1 dose-escalation portion of the trial assessed the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of LNS8801. Data from the study has allowed Linnaeus to determine the RP2D and safely open the phase 2 dose-expansion cohorts. Linnaeus anticipates opening several more phase 2 dose-expansion cohorts exploring LNS8801 activity as a monotherapy and in combination with other compounds in defined patient populations in the coming year.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About LNS8801
LNS8801 is an orally bioavailable and highly specific agonist of GPER whose activity is dependent on the expression of GPER. GPER activation suppresses well-known tumor-associated genes, such as c-Myc and PD-L1. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing phase 1/2 study in humans, LNS8801 monotherapy has been safe and well-tolerated. Additionally, LNS8801 has demonstrated target engagement and clinical benefit in advanced cancer patients. Data from the phase 1/2 study is anticipated to be presented in a peer-reviewed setting in 2021.

On October 13, 2020 miR Scientific, LLC, a healthcare company whose purpose is to transform global cancer management by providing early and highly accurate detection, characterization and monitoring of disease, reported that it has received Breakthrough Device Designation by the U.S Food & Drug Administration for its miR Sentinel PCC4 Assay (miR Sentinel Prostate Test) (Press release, miR Scientific, OCT 13, 2020, View Source [SID1234568435]). FDA Breakthrough Device designation is granted to novel medical devices that have the potential to provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.

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The Company’s miR Sentinel Prostate Test is a new method to analyze small non-coding RNAs (sncRNA) derived from a simple, non-invasive urine specimen from age-eligible men. Using only the expression level of these sncRNAs, a proprietary Statistical Classification Algorithm derives scores that classify patients according to the likelihood of being in the following four possible groups: no molecular evidence of prostate cancer; low-risk; intermediate-risk; or high-risk prostate cancer. Initial validation data for the miR Sentinel Prostate Test was published in the September 2020 issue of The Journal of Urology. The Company will initially commercialize its test as a Laboratory Developed Test in the US. Through the Breakthrough Device Program, miR Scientific will work more closely and frequently with the FDA to expedite its review of the miR Sentinel Prostate Test.

In comparison to currently available technologies alone, the specificity, sensitivity and empirical NPV and PPV of the miR Sentinel Prostate Test may significantly reduce mortality and decrease the number of hospitalizations, physician visits and reduce recovery time. The Company designed the miR Sentinel Prostate Test to revolutionize a patient’s disease journey when used by a provider in conjunction with other clinical findings and/or laboratory tests.

"We are highly appreciative that the FDA’s breakthrough designation process provided miR Scientific with invaluable feedback, which we have incorporated into our current clinical prospective studies to support our full marketing authorization plan" said Sam Salman, Chairman and CEO of miR Scientific. "Receiving this designation achieves another important milestone in the development of our novel and ground-breaking technology. We believe that the accuracy and non-invasive feature of our award-winning technology will impact the lives of millions of men and forever positively change the standard of care for urological cancers".

On October 13, 2020 Boehringer Ingelheim reported new data for Gilotrif (afatinib) which further affirm its activity in squamous cell carcinoma of the lung and, in a separate study, epidermal growth factor receptor mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) (Press release, Boehringer Ingelheim, OCT 13, 2020, View Source [SID1234568434]). The findings are being presented at the IASLC 2020 North America Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (NACLC 2020).

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Analysis from a retrospective, real-world study of patients with metastatic squamous NSCLC who progressed on first-line pembrolizumab plus platinum-based chemotherapy provides effectiveness and safety data for afatinib following immunotherapy (IO) in this second-line setting. Median overall time on treatment (TOT) for patients who received second-line afatinib was 7.3 months (95% confidence interval [CI]; 5.2-8.1). Incidence of severe immune-related adverse events (irAEs) occurred in six patients (pneumonitis, colitis, hepatitis). This analysis also evaluated chemotherapy in this second-line setting, with median overall TOT of 4.2 months (95% CI; 3.9-4.9). There were no reported irAES in the chemotherapy cohort.

"Given relatively recent advances with immunotherapy, prospective trials have yet to investigate the use of afatinib following first-line immunotherapy and chemotherapy in metastatic squamous non-small cell lung cancer," said Edward S. Kim, M.D., FACP, Levine Cancer Institute. "Findings from this study suggest that second-line afatinib is generally well-tolerated and effective in patients with metastatic squamous cell carcinoma of the lung when pembrolizumab is added to first-line platinum-based chemotherapy."

In a separate data set presented at the meeting, researchers assessed the use of afatinib in Asian and non-Asian patients with EGFRm+ NSCLC whose tumors have G719X/L861Q/S768I non-resistant mutations, pooled from randomized clinical trials and real-world studies. The analysis showed that afatinib is effective in these patients, and is unaffected by ethnicity (overall response rate: 66% Asian/59% non-Asian; median duration of response: 14.7 months/15.9 months; G719X: 62%/65%; L861Q: 60%/50%; S768I: 80%/25%).

Bjoern Rueter, M.D., Therapeutic Area Head Oncology, USA, at Boehringer Ingelheim, said, "These data sets further expand our understanding of afatinib’s therapeutic profile in metastatic squamous non-small cell lung cancer and among those with EGFR mutation-positive disease. As we continue to take cancer on at Boehringer Ingelheim, our ongoing research is aimed at supporting unmet treatment needs for the lung cancer and broader oncology community through leading science."

Gilotrif is indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have non-resistant EGFR mutations as detected by an FDA-approved test. Gilotrif is also approved for the treatment of patients with advanced squamous cell carcinoma of the lung whose disease has progressed after treatment with platinum-based chemotherapy.

Data Presentations Featured at IASLC NACLC 2020:

Real-world Effectiveness and Safety of Afatinib Following Immunotherapy (IO) in the Treatment of Metastatic, Squamous Cell/Mixed Histology Carcinoma of the Lung: A Multi-site Retrospective Chart Review Trial in the US. Friday October 16, 17:00-18:00 CDT.
Afatinib in Asian and Non-Asian Patients (pts) with EGFR Mutation-positive (EGFRm+) NSCLC Harboring Major Uncommon Mutations Friday October 16, 17:00-18:00 CDT.
What Is Gilotrif?
Gilotrif is a prescription medicine that is used to treat people with non-small cell lung cancer (NSCLC) that:

has certain (non-resistant) abnormal epidermal growth factor receptor (EGFR) gene(s). Your healthcare provider will perform a test to make sure that Gilotrif is right for you.
has spread to other parts of the body (metastatic), and
has not been previously treated for metastatic lung cancer
It is not known if Gilotrif is safe and effective in treating people with lung cancer that has resistant abnormal EGFR genes.

or

is used to treat people with squamous cell lung cancer that:

has spread to other parts of the body, and
has been previously treated with chemotherapy that contains platinum.
It is not known if Gilotrif is safe and effective in children.

Important Safety Information for Gilotrif (afatinib) Tablets

Before you take Gilotrif, tell your doctor if you:

have kidney or liver problems
have lung or breathing problems other than lung cancer
have a history of an ulcer, a tear (perforation) in your stomach or intestine, or diverticular disease (inflammation) in parts of your large intestine
have a history of severe dry eye or any other eye problems. Tell your doctor if you wear contact lenses.
have heart problems
have any other medical conditions
are pregnant or plan to become pregnant. Gilotrif can harm your unborn baby.
Females who are able to become pregnant should use effective birth control during treatment with Gilotrif and for at least 2 weeks after your last dose of GILOTRIF. Talk to your doctor about birth control methods that may be right for you.
Tell your doctor right away if you become pregnant or think you are pregnant during treatment with Gilotrif.
are breastfeeding or plan to breastfeed. It is not known if Gilotrif passes into your breast milk. Do not breastfeed while taking Gilotrif and for 2 weeks after your last dose of Gilotrif. Talk to your doctor about the best way to feed your baby if you take Gilotrif.
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Gilotrif may affect the way other medicines work, and other medicines may affect the way Gilotrif works. Taking certain medicines with Gilotrif may increase your risk of developing a tear (perforation) in your stomach or intestine.

What to avoid while taking Gilotrif
Limit your time in the sun. Gilotrif can make your skin sensitive to sunlight. You could get or have worsening rash or acne. You could get a severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight during treatment with Gilotrif.

Gilotrif may cause serious side effects, including:

Diarrhea. Diarrhea is common with Gilotrif and may sometimes be severe. Severe diarrhea can cause loss of body fluid (dehydration) and kidney problems that can sometimes lead to death. During your treatment with Gilotrif, your doctor should prescribe medicines to treat diarrhea. Take this medicine exactly as your doctor tells you to. Tell your doctor if you have diarrhea. Get medical attention right away if your diarrhea does not go away or becomes severe.
Skin reactions. Gilotrif can cause redness, rash, and acne. It is important to get treatment for skin reactions as soon as you notice them. Take medicines to help skin reactions exactly as your doctor tells you to. Get medical attention right away if you develop severe skin reactions such as peeling or blistering of the skin, or blisters in your mouth.
Lung or breathing problems. Gilotrif may cause inflammation of the lung that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your doctor right away if you have any new or worsening lung problems, or any combination of the following symptoms: trouble breathing or shortness of breath, cough, or fever.
Liver problems. Gilotrif can cause liver problems that can sometimes lead to death. Tell your doctor right away if you have any symptoms of a liver problem which may include:
yellowing of your skin or the white part of your eyes (jaundice)
dark or brown (tea-colored) urine
pain on the upper right side of your stomach area (abdomen)
bleeding or bruising more easily than normal
feeling very tired
Your doctor will do blood tests to check your liver function during your treatment with Gilotrif.

Tear (perforation) in your stomach or intestine. Tears in your stomach or intestine can happen with Gilotrif and can sometimes lead to death. Your risk of developing a tear in your stomach or intestine may be increased if you:
take certain medicines with Gilotrif including: corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and certain other medicines.
have a history of stomach or intestinal ulcers, or if you have had diverticular disease (inflammation in parts of the large intestine).
Get medical help right away if you develop severe stomach-area (abdomen) pain during treatment with Gilotrif.
Eye problems. Tell your doctor right away if you have symptoms of eye problems. Symptoms may include:
eye pain, swelling, redness, or tearing
blurred vision
sensitivity to light
other changes in your vision
Heart problems. Tell your doctor right away if you have any symptoms of a heart problem which may include:
new or worsening shortness of breath while at rest or with activity
cough
tiredness
swelling of your ankles, feet, or legs
feeling that your heart is pounding or racing (palpitations)
sudden weight gain
Your doctor may change your dose, temporarily stop or permanently stop treatment with Gilotrif if you have certain side effects.

The most common side effects of Gilotrif include diarrhea, rash, acne, mouth sores, nail inflammation, dry skin, decreased appetite, nausea, vomiting, and itching.

Gilotrif may cause decreased fertility in females and males. This may affect your ability to have a child. Talk to your doctor if this is a concern for you.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of Gilotrif. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Prescribing Information and Patient Information.

GF CONS ISI 10.21.19

About Boehringer Ingelheim in Oncology
Cancer takes. Takes away time. Takes away loved ones. At Boehringer Ingelheim Oncology, we are giving patients new hope by taking cancer on. We are dedicated to collaborating with the oncology community on a shared journey to deliver leading science. Our primary focus is in lung and gastrointestinal cancers, with the goal of delivering breakthrough, first-in-class treatments that can help win the fight against cancer. Our commitment to innovation has resulted in pioneering treatments for lung cancer and we are advancing a unique pipeline of cancer cell directed agents, immune oncology therapies and intelligent combination approaches to help combat many cancers.

On October 13, 2020 Iksuda Therapeutics (Iksuda), the developer of enhanced, new-generation of Antibody Drug Conjugates (ADCs), reported it has executed its option to secure exclusive, worldwide rights to develop a novel class of tumour-activated prodrug payloads from the University of Goettingen, following a successful collaboration exemplifying the series in ADC formats (Press release, Iksuda Therapeutics, OCT 13, 2020, View Source [SID1234568431]). The highly potent and selective payload series represents a powerful new class within ADC development with novel protein alkylating cytotoxicity. Iksuda will drive onward development and commercialisation, incorporating the tuneable payload series in its ADC pipeline and payload armoury, to create best in class ADC therapeutics for nominated targets associated with haematological and solid tumours with high unmet need.

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The partnership with the University of Goettingen was founded on Iksuda’s commitment to expand its payload armoury and optimise ADC design according to target antigen. The programme confirmed the value of tumour-selective activation of these powerful cytotoxic agents, conjugated with Iksuda’s stable conjugation technology (PermaLink), in widening the therapeutic index of ADCs. The novel protein-alkylating mode-of-action of the payload series differs from the field’s primary focus of intra- or DNA inter-strand cross-linking, conferring benefits against drug resistance mechanisms. Through the combination of PermaLink technology and the protein alkylating prodrugs, the Company aims to enable the differentiated development of more powerful ADCs with improved tumour killing, aligned with improved safety index and an ability to overcome potential tumour resistance.

Iksuda has demonstrated the potential value of prodrug approaches for targeted cancer therapeutics through its recent license of a CD19-targeting ADC from LegoChem Biosciences ("LCB") for hard-to-treat B-cell cancers, including diffuse large B-cell lymphoma and Burkitt lymphoma. The ADC contains LCB’s prodrug DNA-cross-linking payload, with preclinical data confirming an impressive increase in therapeutic index over comparators. Under a broader agreement, the Company has gained access to LCB’s prodrug payload platform for use in nominated Iksuda targets.

Dr Dave Simpson, PhD, Chief Executive Officer, Iksuda Therapeutics, said: "Iksuda’s successful partnership with the University of Goettingen, led by Professor Lutz Tietze, and subsequent licensing agreement demonstrates our continued work in building and refining approaches to ADC development. We are successfully responding to the industry-wide challenge of being able to treat all patients with cancer. Iksuda remains focussed on building a pipeline of next-generation ADCs with improved therapeutic index through our internal and external pipeline, harnessing our deep understanding in the field and accepting the challenge of targeting areas of high unmet clinical need."

Dr Jens-Peter Horst, PhD, Chief Executive Officer, MBM ScienceBridge, the technology transfer organisation of the University of Goettingen, said: "This agreement is exemplary for the successful transfer of many years of academic research and development work into a very promising and innovative cancer therapy."

On October 13, 2020 Lassogen, a company dedicated to developing lasso peptides as an entirely new therapeutic modality, reported that it has raised $4.5 million in an oversubscribed seed round of funding led by Playground Global with participation from Better Ventures, First In Ventures, Tsingyuan Ventures, and additional investors (Press release, Lassogen, OCT 13, 2020, View Source [SID1234568430]). Combined with pre-seed funding in 2019, Lassogen has raised investment capital totaling $5.1 million to date. The seed investment proceeds will enable the company to achieve key results that demonstrate the utility and promise of lasso peptides for treating serious human diseases such as cancer, autoimmunity, pain, and inflammation.

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Lassogen is developing a new class of peptide therapeutics that combine the strengths of antibodies and small molecule drugs while overcoming many of their limitations. Lasso peptides are folded into a unique lariat structure which renders them extraordinarily stable to degradation by proteases, low pH, or high temperatures and provides a three-dimensional array of amino acid side chains to engage targets with high affinity and selectivity. Naturally occurring lasso peptides are diverse in terms of size, shape, and composition, thus offering highly tunable and modular scaffolds for designing novel therapeutics with optimized properties.

Lassogen was founded by CEO Mark Burk, Ph.D., who was previously CEO and founder of Snap Bio, along with co-founder Kent Boles, Ph.D., and academic co-founders and advisors Douglas Mitchell, Ph.D., Professor of Chemistry at University of Illinois Urbana-Champaign, and Tracy Handel, Ph.D., Professor of Pharmaceutical Science at University of California San Diego.

"Lasso peptides represent a rare and powerful new therapeutic modality that could enable breakthrough treatments for challenging diseases by modulation of disease targets that are difficult for antibodies and small molecules. We are benefitting from a confluence of technology advances and insights that revealed the unexpected high prevalence and extreme diversity of lasso peptides produced by bacteria," says co-founder and CEO Mark Burk. "By taking cues from nature, we are now in a position to leverage the modern tools of in silico modeling and synthetic biology, including molecular evolution, to design and rapidly advance optimized lasso peptides into development against a range of high value targets."

"We see an opportunity for Lassogen to create an entirely new class of programmable medicines to treat challenging disease targets," said Peter Barrett, General Partner at Playground Global. "We are delighted to be a part of their journey toward a healthier future."

Phyllis Whiteley, Ph.D., Venture Partner at Playground Global, will join Lassogen’s board of directors. "The majority of therapeutics are dominated by antibodies and small molecules, yet many important diseases are resistant to those treatments," said Whiteley. "The Lassogen team, including serial entrepreneur and operator Mark Burk as well as highly respected academics and technologists, is uniquely positioned to produce and program lasso peptides to treat challenging diseases."

"We’re thrilled to be supporting the important and innovative work that Lassogen is doing, which has the potential to usher in a new era of success against debilitating diseases such as cancer," says Wes Selke, Managing Director at Better Ventures. "Mark and his team have the right backgrounds to make this happen and are exactly the kind of mission-driven founders we seek to back."