On August 27, 2020 Sysmex Inostics, Inc., a global leader and pioneer in blood-based circulating tumor DNA (ctDNA) analysis for oncology, reported the publication of a clinical study evaluating RAS mutation status in circulating tumor DNA (ctDNA) of colorectal cancer (CRC) patients undergoing anti-EGFR antibody therapy (cetuximab or panitumumab) rechallenge using the OncoBEAM RAS CRC test in two different multicenter Japanese retrospective trials, JACCRO CC-08 and JACCRO CC-09 (Press release, Sysmex Inostics, AUG 27, 2020, View Source [SID1234568255]).

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OncoBEAM RAS CRC is a test that uses BEAMing technology, an enhanced digital PCR method optimized for high sensitivity blood-based mutation detection for metastatic colorectal cancer (mCRC) patients. In this study, investigators utilized the highly sensitive nature of OncoBEAM testing to explore the clinical value of monitoring changes in plasma RAS mutations in CRC patients during treatment with anti-EGFR antibody therapy.

Colorectal cancer continues to be one of the leading causes of cancer-related deaths globally. Treatment of mCRC patients with anti-EGFR monoclonal antibodies have demonstrated significant improvements in the survival of patients with wild-type RAS tumors. mCRC patients being considered for anti-EGFR therapy rechallenge could greatly benefit the overall patient survival by undergoing initial plasma testing to establish RAS mutation status at baseline, as well as performing subsequent tests to monitor RAS mutation dynamics during treatment. By receiving regular blood draws throughout the anti-EGFR rechallenge treatment, patients would benefit from periodic OncoBEAM RAS testing, which would in turn deliver valuable insights for clinicians in assessing therapy response.

The study published in JCO Precision Oncology by Sunakawa et al., demonstrated that RAS mutations were found in 38% of CRC patients after receiving the first course of anti-EGFR mAb therapy, but prior to rechallenge treatment. The disease control rate (DCR) was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation detected by OncoBEAM at baseline. The data also showed that patients with RAS mutations detected just before anti- EGFR mAb rechallenge had no survival benefit from rechallenge treatment. Moreover, post-progression survival time after rechallenge was worse in patients with RAS mutations than in patients without mutations at disease progression. The emergence of RAS mutations during rechallenge treatment at disease progression is therefore useful for predicting outcomes of anti- EGFR mAb therapy rechallenge.

"We found that the OncoBEAM RAS CRC assay was not only effective in monitoring the resistance to anti-EGFR therapy, but was also important in helping us determine the efficacy of the rechallenge treatment and therefore predict patients who would have favorable outcomes. Overall, our novel findings support the value of using the ultrasensitive OncoBEAM RAS liquid biopsy test in the clinical management of CRC patients receiving anti-EGFR mAb as rechallenge treatment. " stated Dr. Yu Sunakawa, MD, PhD, Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan.

Besides results of this publication, a new prospective observational trial "REMARRY (UMIN000036424)" has been initiated with over 100 patients recruited as of June 2020. This clinical trial, supported by SCRUM-Japan MONSTAR-SCREEN, will expand the evaluation of patient-specific dynamics in ctDNA RAS mutational status as a predictor of anti-EGFR mAb rechallenge efficacy. Overall, the aggregate results from these trials should strongly support the clinical utility of performing longitudinal plasma OncoBEAM RAS testing in monitoring tumor response during anti-EGFR antibody therapy.

The publication, titled "RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment with Anti-EGFR Antibodies in Patients with Metastatic Colorectal Cancer," was published in JCO Precision Oncology, July 28, 2020, by Yu Sunakawa et al.: View Source

The poster, titled "REMARRY and PURSUIT trials: Liquid biopsy-guided rechallenge of anti-EGFR monoclonal antibody for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer" was presented at ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer 2020 by Hiromi Nakajima et al.: View Source

On August 27, 2020 Lantern Pharma (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") platform to transform the pace, risk and cost of oncology drug discovery and development, and identify patients who will benefit from its targeted oncology drug candidates, reported that Panna Sharma, CEO and President, will provide company updates at the following investor events in September (Press release, Lantern Pharma, AUG 27, 2020, View Source [SID1234568094]):

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The LD Micro 500
Date/Time: September 1, 2020 at 2:40 p.m. ET
MedInvest AI, Big Data & Digital Health Conference
Date/Time: September 9, 2020 at 10:40 a.m. ET
Colliers Institutional Investor Conference
Date/Time: September 10, 2020 at 9:00 a.m. ET to 5:00 p.m. ET (1×1 only; no presentation)
H.C. Wainwright 22nd Annual Global Investor Conference
Date/Time: September 15, 2020 at 4:30 p.m. ET
AI 2020, 13th Annual BioPharm America Conference
Fireside Chat: Using AI to Optimize Drug Selection and Development, hosted by Zacks Investment Research John Vandermosten
Date/Time: September 21, 2020 at 11:45 a.m. ET
All meetings and presentations will be held virtually. Investors and media interested in meeting with Panna Sharma should contact Marek Ciszewski, J.D., at: [email protected] or +1.628.777.3167. Registered conference attendees may also request meetings through the respective conference registration system.

On August 27, 2020 UroGen Pharma Ltd. (Nasdaq: URGN), a biopharmaceutical company dedicated to building and commercializing novel solutions that treat specialty cancers and urologic diseases, reported that the Phase 2 APOLLO clinical trial of a RTGel hydrogel formulation in combination with BOTOX (onabotulinumtoxinA) intravesical instillation in patients with overactive bladder (OAB) and urinary incontinence did not meet the primary endpoint of improvement of overactive bladder symptoms, as measured by the reduction in urinary incontinence episodes per day (Press release, UroGen Pharma, AUG 27, 2020, View Source [SID1234564492]). Data suggests that this result may have been due to BOTOX not effectively permeating the urothelium.

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Safety and tolerability were evaluated compared to placebo, as well as the dwell time manifested by hydrogel excretion. The combination was reported to be safe and well tolerated compared to placebo, with extended dwell time for up to 10 hours following initial instillation. Patients also reported satisfaction with the ease of hydrogel administration which is performed through a standard urinary catheter. A full evaluation of the data is underway, and the companies are working collaboratively on next steps in the partnership.

"In our own research experience, we have clearly demonstrated the ability of RTGel to successfully deliver active molecules to the urothelium resulting in a therapeutic effect. While we were disappointed with the results of the APOLLO trial, the data are very informative and provide important learnings for future experiments," said Dr. Mark Schoenberg, Chief Medical Officer at UroGen. "The topline data from this trial reinforces that our RTGel technology could be combined with a substantial library of molecules to deliver therapy where dwell time may improve outcomes and we look forward to our continued collaboration with AbbVie as they develop their portfolio of toxin proteins."

The Phase 2 trial was conducted by AbbVie under the license agreement entered into with UroGen in October 2016. This agreement granted an exclusive worldwide license to Allergan plc, now an AbbVie company, to research, develop, manufacture, and commercialize pharmaceutical products formulated with an RTGel hydrogel formulation and clostridial toxins, including BOTOX. The license agreement allows the companies to continue exploration of the RTGel hydrogel formulation in combination with AbbVie’s portfolio of clostridial toxins in OAB and other patient populations. UroGen is eligible to receive payments from AbbVie related to the achievement of certain development, regulatory, and commercial milestones, in addition to royalties on potential net sales.

"Our RTGel sustained release technology has repeatedly established its unique ability to reach and remain in body cavities that have long presented treatment challenges to the medical community," said Liz Barrett, President and Chief Executive Officer of UroGen. "With one drug on the market and a second soon to enter a pivotal study, we remain confident that our innovative technology is a true advance and are committed more than ever to find ways in which our novel approach could expand therapy options for patients."

BOTOX injection into the bladder is approved as a pharmacologic therapy for the treatment of overactive bladder in adults when another type of medication (anticholinergic) does not work well enough or cannot be taken. UroGen’s innovative, hydrogel-based technology platform is designed to enable longer exposure to active pharmaceutical ingredients. Jelmyto (mitomycin) for pyelocalyceal solution, which utilizes the RTGel technology, was recently approved in the U.S. for the treatment of adults with low-grade upper tract urothelial cancer.

About the Phase 2 APOLLO Trial
The trial is a multi-center, randomized, double-blind, placebo-controlled, single-treatment, two-stage, dose-finding clinical trial on patients with overactive bladder with urgency urinary incontinence who have an inadequate response to or are intolerant to pharmacologic therapy. The first stage of the trial is a placebo-controlled, dose escalation design, followed by the second stage, a randomized, placebo-controlled design. Patients received a single bladder instillation of an RTGel hydrogel formulation in combination with BOTOX. The primary efficacy endpoint is the improvement of overactive bladder symptoms as measured by the reduction in urinary incontinence episodes per day.

BOTOX Indication and Important Safety Information

Indication
BOTOX is a prescription medicine that is injected into the bladder muscle and used to treat overactive bladder symptoms such as a strong need to urinate with leaking or wetting accidents, going too often, and the strong, sudden need to go in adults 18 years and older when another type of medication (anticholinergic) does not work well enough or cannot be taken.

IMPORTANT SAFETY INFORMATION
BOTOX may cause serious side effects that can be life threatening. Get medical help right away if you have any of these problems any time (hours to weeks) after injection of BOTOX:

Problems swallowing, speaking, or breathing, due to weakening of associated muscles, can be severe and result in loss of life. You are at the highest risk if these problems are pre-existing before injection. Swallowing problems may last for several months
Spread of toxin effects. The effect of botulinum toxin may affect areas away from the injection site and cause serious symptoms including: loss of strength and all-over muscle weakness, double vision, blurred vision and drooping eyelids, hoarseness or change or loss of voice, trouble saying words clearly, loss of bladder control, trouble breathing, and trouble swallowing
BOTOX may cause loss of strength or general muscle weakness, vision problems, or dizziness within hours to weeks of taking BOTOX. If this happens, do not drive a car, operate machinery, or do other dangerous activities.

Do not receive BOTOX if you: are allergic to any of the ingredients in BOTOX (see Medication Guide for ingredients); had an allergic reaction to any other botulinum toxin product such as Myobloc (rimabotulinumtoxinB), Dysport (abobotulinumtoxinA), or Xeomin (incobotulinumtoxinA); have a skin infection at the planned injection site.

Do not receive BOTOX for the treatment of urinary incontinence if you: have a urinary tract infection (UTI) or cannot empty your bladder on your own (and are not routinely catheterizing). Due to the risk of urinary retention (difficulty fully emptying the bladder), only patients who are willing and able to initiate self-catheterization post treatment, if required, should be considered for treatment.
In clinical trials, 36 of the 552 patients had to self-catheterize for urinary retention following treatment with BOTOX compared to 2 of the 542 treated with placebo. Patients with diabetes mellitus treated with BOTOX were more likely to develop urinary retention than nondiabetics.

The dose of BOTOX is not the same as, or comparable to, another botulinum toxin product.

Serious and/or immediate allergic reactions have been reported including itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness or feeling faint. Get medical help right away if you experience symptoms; further injection of BOTOX should be discontinued.

Tell your doctor about all your muscle or nerve conditions such as ALS or Lou Gehrig’s disease, myasthenia gravis, or Lambert-Eaton syndrome, as you may be at increased risk of serious side effects including difficulty swallowing and difficulty breathing from typical doses of BOTOX.

Tell your doctor about all your medical conditions, including if you: have or have had bleeding problems; have plans to have surgery; had surgery on your face; weakness of forehead muscles; trouble raising your eyebrows; drooping eyelids; any other abnormal facial change; have symptoms of a urinary tract infection (UTI) and are being treated for urinary incontinence (symptoms of a urinary tract infection may include pain or burning with urination, frequent urination, or fever); have problems emptying your bladder on your own and are being treated for urinary incontinence; are pregnant or plan to become pregnant (it is not known if BOTOX can harm your unborn baby); are breastfeeding or plan to (it is not known if BOTOX passes into breast milk).

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using BOTOX with certain other medicines may cause serious side effects. Do not start any new medicines until you have told your doctor that you have received BOTOX in the past.
Tell your doctor if you have received any other botulinum toxin product in the last 4 months; have received injections of botulinum toxin such as Myobloc, Dysport, or Xeomin in the past (tell your doctor exactly which product you received); have recently received an antibiotic by injection; take muscle relaxants; take an allergy or cold medicine; take a sleep medicine; take aspirin-like products or blood thinners.

Other side effects of BOTOX include: dry mouth, discomfort or pain at the injection site, tiredness, headache, neck pain, eye problems: double vision, blurred vision, decreased eyesight, drooping eyelids, swelling of your eyelids, dry eyes; drooping eyebrows; and upper respiratory tract infection. In people being treated for urinary incontinence, other side effects include: urinary tract infection, painful urination, and/or inability to empty your bladder on your own. If you have difficulty fully emptying your bladder after receiving BOTOX, you may need to use disposable self-catheters to empty your bladder up to a few times each day until your bladder is able to start emptying again.
For more information, refer to the Medication Guide or talk with your doctor.

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.

On August 27, 2020, Odonate Therapeutics, Inc. (the "Company") reported that it entered into an underwriting agreement ("Underwriting Agreement") with Jefferies LLC, as the representative of the underwriters named therein (the "Underwriters"), to issue and sell 5,614,036 shares of the Company’s common stock at a public offering price of $14.25 per share (the "Offering") (Filing, 8-K, Odonate Therapeutics, AUG 27, 2020, View Source [SID1234564237]). In addition, the Company granted the underwriters a 30-day option to purchase up to an additional 842,105 shares of its common stock on the same terms and conditions (the "Option"). On August 31, 2020, the Underwriters exercised the Option in full. The Offering and the Option closed on September 1, 2020. The aggregate gross proceeds from the Offering and the Option were $92.0 million before deducting underwriting discounts and offering expenses.

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The securities described above were offered pursuant to a shelf registration statement (File No. 333-233990), which became effective on October 18, 2019. A final prospectus supplement dated August 27, 2020 relating to and describing the terms of the offering was filed with the U.S. Securities and Exchange Commission on August 31, 2020.

In the Underwriting Agreement, the Company agreed to indemnify the underwriters against certain liabilities, including liabilities under the Securities Act of 1933, as amended, or to contribute payments that the underwriters may be required to make because of such liabilities.

A copy of the Underwriting Agreement is attached as Exhibit 1.1 hereto and is incorporated herein by reference. The foregoing description of the Underwriting Agreement does not purport to be complete and is qualified in its entirety by reference to such exhibit.

On August 27, 2020 Massachusetts General Hospital reported that Selpercatinib (Retevmo), a drug targeted precisely against cancers driven by mutations or alterations in the gene RET, was effective in a clinical trial at shrinking tumors in patients with medullary thyroid cancer, with a majority of patients living for more than a year without disease progression (Press release, Massachusetts General Hospital, AUG 27, 2020, View Source [SID1234564160]).

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The drug was effective both in patients with no prior treatment with targeted anti-cancer drugs and in those who had disease progression following treatment with other multitargeted agents, report Lori J. Wirth, MD, investigator in the Massachusetts General Hospital (MGH) Cancer Center, and colleagues.

"What we’re seeing is a combination of very good efficacy and also very good tolerability with selpercatinib," says Wirth. "The response rates are high, responses are very durable, and overall the drug does not cause a lot of toxicity."

Wirth is the lead author of a study published in the New England Journal of Medicine reporting results of the phase 1/2 trial. The trial formed the basis for the approval of selpercatinib by the US Food and Drug Administration in May 2020 for adults and children 12 and older with advanced or metastatic RET-mutated medullary thyroid cancer who require systemic therapy, adults with metastatic RET-driven non-small cell lung cancer, and patients 12 and older with advanced or metastatic RET-fusion positive thyroid cancer resistant to radioactive iodine who require systemic therapy.

Selpercatinib is the first approved drug of its kind targeted specifically to cancers driven by mutations or alterations in the gene RET. Mutations in RET are responsible for up to 70 percent of medullary thyroid cancers (MTC), while RET gene fusions (abnormal combinations of parts of two different genes) account for one-to-two percent of all non-small cell lung cancers and ten-to-twenty percent of other thyroid cancers.

Physicians typically treat patients with RET-associated cancers with drugs that target RET and multiple other enzymes (kinases) commonly found in many different types of cancer. But the two multi-kinase inhibitors currently approved for treatment of medullary thyroid cancer, vandetanib and cabozantinib, have substantial off-target side effects that limit their use in patients with RET-driven cancers.

"If you have a clean, RET-specific inhibitor such as selpercatinib, then you can really pound down RET very strongly and hit the driver alteration much harder, with a better side effect profile," Wirth explains.

In the trial objective response rates, a measure of significant and clinically important tumor shrinkage, were 69 percent for patients with RET-mutated medullary thyroid cancers treated with selpercatinib who had previously received vandetanib, cabozantinib, or both; 73 percent in similar patients who had not received either of the other drugs; and 79 percent for patients with previously treated RET fusion-positive thyroid cancers.

In all, 82 percent of previously treated patients with medullary thyroid cancer, and 92 percent of patients who had not received either vandetanib or cabozantinib lived for at least one year without further disease progression.

The most common side effects with selpercatinib were high blood pressure, increased liver enzyme levels, decrease in sodium levels, and diarrhea, all of which were manageable. Only four of 162 patients had to stop selpercatinib because of side effects.

Wirth and colleagues have launched an international phase-three trial comparing selpercatinib with either vandetanib or cabozantinib as first-line therapy for RET-mutated medullary thyroid cancer.

Additional co-investigators include Jochen Lorch, MD, Dana-Farber Cancer Institute, Boston; Eric Sherman, MD and Alexander Drilon, MD, Memorial Sloan Kettering Cancer Center, NYC; Bruce Robinson, MD, Royal North Shore Hospital, St. Leonards, NSW and Benjamin Solomon MB, BS, PhD, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia; Hyunseok Kang, MD, UC San Francisco; Jonathan W. Goldman, MD, UCLA; Viola W. Zhu, MD, UC Irvine; Francis Worden, MD, U Michigan, Ann Arbor; Nehal Lakhani, MD, PhD, START Midwest, Grand Rapids, MI; Marcia Brose MD, PhD U Pennsylvania, Philadelphia; Jyoti Patel, MD, U Chicago; Sophie Leboulleux, MD, Institut Gustave Roussy, Villejuif, Yann Godbert, MD, Institut Bergonie, Bordeaux, (Y.G.), Fabrice Barlesi, MD, PhD, Aix Marseille University, Christelle de la Fouchardiere, MD, Centre Leon Berard, Lyon, and Jacques Medioni, MD, PhD, Hopital Europeen Georges-Pompidou, all in France; John C. Morris, MD, Mayo Clinic, Rochester, MN; Taofeek K. Owonikoko, MD, PhD, Emory University, Atlanta; Daniel S.W. Tan, M.B., B.S, National Cancer Center Singapore; Oliver Gautschi, MD University of Bern, and Cantonal Hospital of Lucerne, Switzerland; Jared Weiss, MD UNC, Chapel Hill; Mark E. Burkard, MD, PhD, U Wisconsin, Madison; Janessa Laskin, MD, British Columbia Cancer Agency, Vancouver, Canada; Matthew H. Taylor, MD, OHSU, Portland; Matthias Kroiss, MD, Universitatsklinikum Wurzburg, Germany; Todd M. Bauer, MD Sarah Cannon Research Institute–Tennessee Oncology, Nashville; Benjamin Levy, MD, Johns Hopkins Kimmel Cancer Center, Washington, DC; Victor Moreno, MD, PhD, Fundacion Jimenez Diaz, Madrid, Spain; Kevin Ebata, PhD, Michele Nguyen, B.S., Dana Heirich, MSN, Edward Y. Zhu, PhD, Xin Huang, PhD, Luxi Yang, MS, Jennifer Kherani, MD, and S. Michael Rothenberg, MD, PhD, Loxo Oncology, Stamford, CT: Vivek Subbiah, MD and Maria E. Cabanillas, MD, UT MD Anderson Cancer Center, Houston; and Manisha H. Shah, MD, Ohio State University Comprehensive Cancer Center, Columbus.

The trial was supported by Loxo Oncology, a wholly owned subsidiary of Eli Lilly and Company. Dr. Wirth discloses a consulting or advisory role with Loxo Oncology, Eli Lilly and Company, and other companies.