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Kura Oncology’s Menin-MLL Inhibitor KO-539 Receives Orphan Drug Designation from FDA for Treatment of Acute Myeloid Leukemia

On July 24, 2019 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the Company’s menin-mixed lineage leukemia (menin-MLL) inhibitor KO-539 for the treatment of acute myeloid leukemia (AML) (Press release, Kura Oncology, JUL 24, 2019, View Source [SID1234537702]).

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"Orphan Drug Designation for AML represents a significant milestone in the development of KO-539," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "This decision by the FDA follows the clearance of our investigational new drug (IND) application in March 2019 and recognizes the potential for KO-539 to address a high unmet need for patients suffering from AML. We are very encouraged by our preclinical data in genetically defined subsets, such as tumors with MLL fusions and rearrangements and NPM1 mutations, and we are in the final stages of study startup for our Phase 1 clinical trial in relapsed or refractory AML."

The FDA’s Orphan Drug Designation program provides orphan status to drugs defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. Orphan Drug Designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and seven-year marketing exclusivity upon FDA approval.

About KO-539

KO-539 is a potent and selective small molecule inhibitor of the menin-MLL protein-protein interaction. MLL-rearranged leukemias are characterized by chromosomal translocations of the MLL gene that are primarily found in patients with AML and acute lymphoblastic leukemia (ALL). These translocations form oncogenes encoding MLL fusion proteins, which play a causative role in the onset, development and progression of MLL-rearranged leukemias. The target genes of the MLL fusion proteins are also found to be overexpressed in a broader subset of AMLs characterized by oncogenic driver mutations in genes such as NPM1. These mutations also appear to be dependent on the interaction between menin and MLL, suggesting that the menin-MLL complex is a central node in epigenetic dysregulation driven by distinct oncogenic driver mutations known to be important in AML and other hematologic malignancies. In preclinical studies, KO-539 has demonstrated potent and selective inhibition of the proliferation of MLL-rearranged leukemia cell lines. Kura has also generated preclinical data showing robust and durable efficacy in multiple in vivo models of AML characterized by MLL-rearrangements or oncogenic driver mutations in genes such as NPM1.

DelMar Pharmaceuticals Enrolls First Patient in the Recently-Approved Adjuvant Setting Arm of Phase 2 Study of VAL-083 for the Treatment of MGMT-Unmethylated Glioblastoma Multiforme

On July 24, 2019 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of novel cancer therapies, reported that the first patient has been treated in the adjuvant (pre-temozolomide maintenance) trial arm of VAL-083’s Phase 2 study in MGMT-unmethylated glioblastoma multiforme (GBM) being conducted at the University of Texas MD Anderson Cancer Center (MDACC) (Press release, DelMar Pharmaceuticals, JUL 24, 2019, View Source [SID1234537701]). This recently-approved arm of the study will enroll up to 24 newly-diagnosed patients who have undergone surgery and chemoradiation with temozolomide (TMZ) but will now receive VAL-083 in place of standard of care TMZ for adjuvant therapy.

"Treating patients with MGMT promoter unmethylated glioblastoma is particularly challenging," commented principal investigator Dr. Barbara O’Brien, assistant professor of Neuro-Oncology at the MD Anderson Cancer Center. "These tumors are inherently resistant to temozolomide, leaving physicians and patients without viable alternative treatments, so I’m particularly pleased that we have added this additional trial arm to our ongoing study. Better therapies are greatly needed for both newly-diagnosed and recurrent glioblastoma, and VAL-083 has so far shown a favorable safety profile and provided early, but encouraging, results from the trial that is currently underway."

This adjuvant arm, which was recently approved by the MDACC Institutional Review Board, will provide early disease data on VAL-083, in contrast to those patients enrolling in the Company’s original recurrent trial arm of the MDACC clinical study who have typically been heavily pre-treated with TMZ prior to disease recurrence. In the recurrent setting, the Company previously announced that MDACC had approved up to 35 additional patients to this recurrent GBM study at a dose of 30 mg/m2, allowing for a total of up to 83 patients to be enrolled. To date, 56 recurrent patients have been enrolled. DelMar is actively enrolling patients for both trial arms of the clinical study at MDACC.

Concurrently, the Company is conducting a Phase 2 clinical study of VAL-083 as first line treatment for GBM in combination with radiotherapy in China at the renowned Sun Yat-sen University Cancer Center for which it provided an update on June 3, 2019. This update can be accessed via the company’s website at View Source VAL-083 has been granted orphan drug designations by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. It has also been granted fast-track status for the treatment of recurrent GBM by the U.S. FDA.

"Enrolling and treating the first adjuvant patient in this study is an important milestone as it provides us with the opportunity to understand the best use for VAL-083 in the clinical setting – whether as first-line therapy along with radiation, as adjuvant therapy immediately following chemoradiation or in the recurrent setting. We firmly believe in the potential for this compound and look forward to providing an opportunity for a larger patient population to benefit from VAL-083 treatment. We look forward to providing updates on the progress of all of our clinical programs," commented Saiid Zarrabian, DelMar’s Chief Executive Officer.

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class", bifunctional DNA-targeting agent that introduces inter-strand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute (NCI). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance, including MGMT, in cancer cell models and animal studies. Further details regarding these studies can be found at:

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Aura Biosciences to Present Long-Term Clinical Data for AU-011 at the 37th Annual Scientific Meeting of the American Society of Retina Specialists

On July 24, 2019 Aura Biosciences, a leader in the development of novel targeted therapies in ocular oncology, reported that two-year clinical data from its ongoing Phase 1b/2 clinical trial evaluating the safety and efficacy of light-activated AU-011, the Company’s lead product candidate for the treatment of primary choroidal melanoma, reported that it will be highlighted in an oral presentation at the 37th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS) being held July 26- 30, 2019 in Chicago, Illinois (Press release, Aura Biosciences, JUL 24, 2019, View Source [SID1234537700]).

"There is an urgent unmet medical need for targeted treatment options for patients suffering from primary choroidal melanoma, a life-threatening form of eye cancer," said Amy C. Schefler, M.D., Associate Professor of Clinical Ophthalmology, Weill Cornell Medical College/Houston Methodist Hospital and the University of Texas Health Science Center. "Emerging results from the Phase 1b/2 trial of light-activated AU-011 demonstrate tumor control and visual acuity preservation, warranting continued development of the program."

Title: Two-Year Results of an Ongoing Phase 1b/2 Open Label Clinical Trial of AU-011 for the Primary Treatment of Small to Medium Choroidal Melanoma,

Presenter: Amy C. Schefler, M.D., Associate Professor of Clinical Ophthalmology, Weill Cornell Medical College/Houston Methodist Hospital and the University of Texas Health Science Center

Session: Ocular Oncology Symposium

Date and time: Monday, July 29, 2019; 9:35 -9:41am CDT

About Choroidal Melanoma

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary intraocular tumor in adults and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes in approximately 50 percent of cases with liver involvement in 80-90% of cases and, unfortunately, metastatic disease is universally fatal (source: OMF). There is a very high unmet need for a new vision sparing targeted therapy that could enable early treatment intervention for this life-threatening rare disease given the lack of approved therapies, and the comorbidities of radioactive treatment options.

About Light-Activated AU-011

AU-011 is a first-in-class targeted therapy in development for the treatment of primary choroidal melanoma. The therapy consists of proprietary viral-like particle bioconjugates (VPB) that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the cell membrane of tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.

Anixa Biosciences Announces Additional Patent Issued on Cancer Detection Technology

On July 24, 2019 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on harnessing the body’s immune system to fight cancer, reported that the United States Patent and Trademark Office (USPTO) has issued US Patent No. 10,360,499, a key component of Anixa’s Cchek technology for early detection of cancer (Press release, Anixa Biosciences, JUL 24, 2019, View Source [SID1234537699]).

This patent provides broader coverage for the use of Anixa’s technology in a wider range of applications and protects critical new improvements developed for Anixa’s cancer detection technology, utilizing flow cytometry and artificial intelligence.

"The claims of this patent were allowed in March of this year as noted in a previous announcement, and we are pleased that this key patent has finally been issued," stated Dr. Amit Kumar, President and CEO of Anixa. "We are pleased to receive further patent protection on our liquid biopsy technology and look forward to launching a prostate cancer confirmatory test as the first product utilizing this technology later this year."

The patent is titled, "METHODS FOR USING ARTIFICIAL NEURAL NETWORK ANALYSIS ON FLOW CYTOMETRY DATA FOR CANCER DIAGNOSIS." Inventors of the patent include Dr. Amit Kumar, John Roop, Anthony Campisi, and Dr. George Dominguez. This patent is held exclusively by Anixa and is not licensed to any third parties.

Alexion Reports Second Quarter 2019 Results

On July 24, 2019 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported financial results for the second quarter of 2019 (Press release, Alexion, JUL 24, 2019, View Source [SID1234537698]). Total revenues in the second quarter were $1,203.3 million, a 15 percent increase compared to the same period in 2018. The negative impact of foreign currency on total revenues year-over-year was 1 percent, or $15.1 million, inclusive of hedging activities. On a GAAP basis, diluted EPS in the quarter was $2.04, a 200 percent increase versus the prior year. The second quarter of 2018 included $803.7 million of expense related to the value of the in-process research and development asset acquired in connection with our acquisition of Wilson Therapeutics AB. Non-GAAP diluted EPS for the second quarter of 2019 was $2.64, a 28 percent increase versus the second quarter of 2018.

"We delivered another strong quarter, with continued growth driven by the successful U.S. launches of ULTOMIRIS in PNH and SOLIRIS in gMG. We received three regulatory approvals over the last month, including SOLIRIS for NMOSD in the U.S., and ULTOMIRIS for PNH in Japan and the EU. In addition, the FDA granted priority review for ULTOMIRIS in atypical HUS," said Ludwig Hantson, Ph.D., Chief Executive Officer of Alexion. "We are well positioned to continue our momentum in the second half of 2019, strengthening our four durable franchises in hematology and nephrology, neurology, metabolics and FcRn, advancing and expanding our pipeline, and serving more people living with rare diseases than ever before."

Second Quarter 2019 Financial Highlights

Total net product sales were $1,202.5 million in the second quarter of 2019, compared to $1,044.7 million in the second quarter of 2018.
SOLIRIS (eculizumab) net product sales were $980.8 million, compared to $898.2 million in the second quarter of 2018, representing a 9 percent increase. SOLIRIS volume increased 17 percent year-over-year. SOLIRIS net product sales for the second quarter 2019 included a $31.6 million reduction to revenue related to a recent judicial order on SOLIRIS pricing in Canada. The reduction in revenue includes the impact for the period from September 2017 to June 2019.
ULTOMIRIS (ravulizumab-cwvz) net product sales were $54.2 million in the second quarter of 2019.
STRENSIQ (asfotase alfa) net product sales were $141.3 million, compared to $125.1 million in the second quarter of 2018, representing a 13 percent increase. STRENSIQ volume increased 21 percent year-over-year.
KANUMA (sebelipase alfa) net product sales were $26.2 million, compared to $21.4 million in the second quarter of 2018, representing a 22 percent increase. KANUMA volume increased 33 percent year-over-year.
GAAP cost of sales was $99.2 million, compared to $95.3 million in the second quarter of 2018. Non-GAAP cost of sales was $95.7 million, compared to $89.3 million in the second quarter of 2018.
GAAP R&D expense was $187.6 million, compared to $173.4 million in the second quarter of 2018. Non-GAAP R&D expense was $148.7 million, compared to $158.3 million in the second quarter of 2018.
GAAP SG&A expense was $299.3 million, compared to $277.3 million in the second quarter of 2018. Non-GAAP SG&A expense was $255.8 million, compared to $230.4 million in the second quarter of 2018.
GAAP acquired in-process research and development expense (benefit) was $(4.1) million related to the agreement of the final working capital adjustment for the Syntimmune, Inc. acquisition, compared to $803.7 million in the second quarter of 2018, related to the in-process research and development asset acquired in connection with the 2018 acquisition of Wilson Therapeutics AB.
GAAP income tax expense was $39.7 million, compared to income tax expense of $38.8 million in the second quarter of 2018. Non-GAAP income tax expense was $90.2 million, compared to $77.1 million in the second quarter of 2018.
GAAP diluted EPS was $2.04, compared to $(2.05) in the second quarter of 2018. The second quarter of 2018 included $803.7 million of expense related to the value of the in-process research and development asset acquired in connection with the Wilson Therapeutics AB acquisition. Non-GAAP diluted EPS was $2.64, compared to $2.07 in the second quarter of 2018.
Research and Development

PHASE 3

SOLIRIS – Neuromyelitis Optica Spectrum Disorder (NMOSD): In June 2019, the U.S. Food and Drug Administration (FDA) approved SOLIRIS for adults with anti-aquaporin-4 (AQP4) auto antibody-positive NMOSD. Applications for approval in the European Union (EU) and Japan are under review. Alexion plans to initiate a Phase 3 study in children and adolescents with NMOSD by the end of 2019.
SOLIRIS – Generalized Myasthenia Gravis (gMG): Dosing is underway in a Phase 3 study of SOLIRIS in children and adolescents with gMG.
ULTOMIRIS – Paroxysmal Nocturnal Hemoglobinuria (PNH): ULTOMIRIS was approved for adults with PNH in Japan in June 2019 and in the EU in July 2019. A Phase 3 study of ULTOMIRIS in children and adolescents with PNH is underway.
ULTOMIRIS – Atypical Hemolytic Uremic Syndrome (aHUS): In June 2019, Alexion announced that the FDA granted priority review for ULTOMIRIS in aHUS and set a Prescription Drug User Fee Act (PDUFA) target action date of October 19, 2019. The filing was based on previously announced positive topline results from a Phase 3 study of ULTOMIRIS in complement inhibitor-naïve patients with aHUS. Alexion plans to file for regulatory approvals in the EU and Japan in the second half of 2019. In addition, a Phase 3 study of ULTOMIRIS in children and adolescents with aHUS is underway.
ULTOMIRIS – Subcutaneous: Dosing is underway in a single, PK-based Phase 3 study of ULTOMIRIS delivered subcutaneously once per week to support registration in PNH and aHUS. Data are expected in early 2020.
ULTOMIRIS – gMG: Dosing is underway in a Phase 3 study of ULTOMIRIS in gMG.
ULTOMIRIS – NMOSD: Alexion plans to initiate a Phase 3 study of ULTOMIRIS in NMOSD by the end of 2019, pending regulatory feedback.
ULTOMIRIS – Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA): Alexion plans to initiate a Phase 3 study of ULTOMIRIS in HSCT-TMA in the first half of 2020, pending regulatory feedback.
ALXN1840 (WTX101) – Wilson Disease: Dosing is underway in a Phase 3 study of ALXN1840 (WTX101) in Wilson disease, a rare genetic disorder with devastating hepatic and neurological consequences. ALXN1840 is a first-in-class oral copper-binding agent with a unique mechanism of action to bind serum copper and promote its removal from the liver. Enrollment is expected to complete in early 2020.
PHASE 1/2

ALXN1830 (SYNT001): Alexion plans to initiate a Phase 2/3 study of ALXN1830 (SYNT001) in warm autoimmune hemolytic anemia (WAIHA) in early 2020. In addition, Alexion plans to initiate a Phase 1 study of a subcutaneous formulation of ALXN1830 in healthy volunteers in early 2020. Pending results from the Phase 1 study, Alexion plans to initiate a Phase 2/3 study of subcutaneous ALXN1830 in gMG in 2020.
ALXN1810 – Subcutaneous: Alexion has completed a Phase 1 study of subcutaneous ALXN1210 co-administered with Halozyme’s ENHANZE drug-delivery technology, recombinant human hyaluronidase enzyme (rHuPH20), a next-generation subcutaneous formulation called ALXN1810. Strategic planning for the best development path for ALXN1810 is ongoing.
ULTOMIRIS – Amyotrophic Lateral Sclerosis (ALS): Alexion plans to initiate a proof-of-concept study for ULTOMIRIS in ALS in early 2020, pending regulatory feedback.
ULTOMIRIS – Primary Progressive Multiple Sclerosis (PPMS): Alexion plans to initiate an exploratory clinical study of ULTOMIRIS in PPMS.
Caelum Biosciences – CAEL-101 – Light Chain (AL) Amyloidosis: Alexion is collaborating with Caelum Biosciences to develop CAEL-101 for AL amyloidosis, a rare systemic disorder that causes misfolded immunoglobulin light chain protein to build up in and around tissues, resulting in progressive and widespread organ damage. CAEL-101 is a first-in-class amyloid fibril targeted therapy designed to improve organ function by reducing or eliminating amyloid deposits in patients with AL amyloidosis. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in patients with relapsed and refractory AL amyloidosis. Pending regulatory feedback, a Phase 2/3 study investigating CAEL-101 as an add-on to current standard-of-care therapy is planned to begin in 2020.
Affibody AB – ABY-039: In April 2019, Alexion entered into a partnership with Affibody AB, following approval from the relevant regulatory authorities, to co-develop ABY-039 for rare Immunoglobulin G (IgG)-mediated autoimmune diseases. Currently in Phase 1 development, ABY-039 is a bivalent antibody-mimetic that targets the neonatal Fc receptor (FcRn). ABY-039 has been specifically designed to combine Affibody’s protein therapeutics platform (Affibody molecules) and AlbumodTM technology to achieve a long half-life, which, along with its small size provides the potential for less frequent, convenient, at-home subcutaneous administration.
PRE-CLINICAL

ALXN1720: In June 2019, Alexion submitted the initial Clinical Trial Authorization (CTA) application to the Medicines and Healthcare Products Regulatory Agency (MHRA) for the initiation of a Phase 1 study of ALXN1720, a novel anti-C5 albumin-binding bi-specific mini-body that binds and prevents activation of human C5. Alexion plans to initiate this first-in-human study in late 2019.
Zealand Pharma A/S: Alexion is collaborating with Zealand Pharma A/S to discover and develop novel peptide therapies for up to four targets in the complement pathway. Peptides offer a number of advantages, including being highly selective and potent, allowing low dosage volumes for ease of administration, and having the potential to treat a broad range of complement-mediated diseases.
Dicerna – GalXCTM: Alexion is collaborating with Dicerna Pharmaceuticals to jointly discover and develop up to four subcutaneously delivered GalXCTM RNA interference (RNAi) candidates, currently in pre-clinical development, for the treatment of complement-mediated diseases.
Complement Pharma – CP010: Alexion is collaborating with Complement Pharma to co-develop CP010, a pre-clinical C6 inhibitor that has the potential to treat multiple neurological disorders.
2019 Financial Guidance
Alexion is increasing total revenues and EPS guidance. Full guidance updates are outlined below.

Updated 2019 financial guidance assumes a GAAP effective tax rate of 6 to 7 percent and a non-GAAP effective tax rate of 14 to 15 percent.

Alexion’s financial guidance is based on current foreign exchange rates net of hedging activities and does not include the effect of acquisitions, license and collaboration agreements, intangible asset impairments, litigation charges, changes in fair value of contingent consideration or restructuring and related activity outside of the previously announced activities that may occur after the issuance of this press release.

Conference Call/Webcast Information:
Alexion will host a conference call/audio webcast to discuss the second quarter 2019 results today at 8:00 a.m. Eastern Time. To participate in the call, dial 866-762-3111 (USA) or 210-874-7712 (International), conference ID 5564357 shortly before 8:00 a.m. Eastern Time. A replay of the call will be available for a limited period following the call. The audio webcast can be accessed on the Investor page of Alexion’s website at: View Source