On July 14, 2022 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, reported the sale of 30% of the company’s royalty interest from Kyowa Kirin Co., Ltd on the future sales of Crysvita (burosumab) in the United States (U.S.) and Canada to OMERS, one of Canada’s largest defined benefit pension plans, for $500 million (Press release, Ultragenyx Pharmaceutical, JUL 14, 2022, View Source [SID1234616683]). OMERS’ right to receive royalty payments is based on net sales of the product beginning in April 2023 and total payments are capped at 1.45 times the purchase price.

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"In North America, Crysvita has generated more than $1.3 billion net sales in the first four years on the market making it one of the most successful launches in the rare disease field. This non-dilutive financing bolsters Ultragenyx’s balance sheet, funds the ongoing commercialization of multiple approved medicines and the advancement of our diverse clinical pipeline," said Mardi Dier, Chief Financial Officer of Ultragenyx. "We are pleased to partner with OMERS on this transaction who, like us, recognizes the ongoing and future value of Crysvita, the tremendous success of the launch and the significance for patients who will continue to benefit from this important medicine."

"Ultragenyx has successfully launched Crysvita, meaningfully improving the lives of thousands of pediatric and adult patients with two rare diseases. We are proud to invest in a product that has made a difference for so many and that aligns with the investment strategy at OMERS," said Rob Missere, Managing Director and Head of Life Sciences, OMERS Capital Markets. "This deal furthers our mandate of delivering steady, long-term returns to our more than 541,000 members."

Cowen acted as exclusive financial advisor to Ultragenyx on the transaction. Gibson Dunn LLP acted as legal advisor to Ultragenyx. Davies Ward Phillips & Vineberg LLP and Latham & Watkins LLP acted as legal advisors to OMERS.

About Crysvita

Crysvita (burosumab) is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Kirin, against the phosphaturic hormone FGF23. FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting in TIO and other hypophosphatemic conditions, including XLH, is caused by excessive levels and activity of FGF23. Crysvita is designed to bind to and thereby inhibit the biological activity of FGF23. By blocking excess FGF23 in patients with TIO and XLH, Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of vitamin D, which enhances intestinal absorption of phosphate and calcium.

In North America, Crysvita is approved by the U.S. Food and Drug Administration (FDA) and by Health Canada for the treatment of X-linked hypophosphatemia (XLH) and FGF23-related hypophosphatemia in tumor induced osteomalacia (TIO).

Kyowa Kirin and Ultragenyx have been collaborating in the development and commercialization of Crysvita globally based on the collaboration and license agreement between the parties.

U.S. INDICATION
Crysvita (burosumab-twza) is a fibroblast growth factor 23 (FGF23)-blocking antibody indicated for the treatment of:

X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.
FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

With oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol).
When serum phosphorus is within or above the normal range for age.
In patients with severe renal impairment or end stage renal disease.
WARNINGS AND PRECAUTIONS

Hypersensitivity

Discontinue Crysvita if serious hypersensitivity reactions occur and initiate appropriate medical treatment.
Hyperphosphatemia and Risk of Nephrocalcinosis

For patients already taking Crysvita, dose interruption and/or dose reduction may be required based on a patient’s serum phosphorus levels.
Patients with TIO who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia.
Injection Site Reactions

Discontinue Crysvita if severe injection site reactions occur and administer appropriate medical treatment.
ADVERSE REACTIONS
Pediatric XLH Patients

Adverse reactions reported in 10% or more of Crysvita-treated pediatric XLH patients across all studies are: pyrexia, injection site reaction, cough, vomiting, pain in extremity, headache, tooth abscess, dental caries, diarrhea, vitamin D decreased, toothache, constipation, myalgia, rash, dizziness, and nausea.
Post-marketing experience reported in pediatric XLH patients receiving Crysvita – blood phosphorus increased.
Adult XLH Patients

Adverse reactions reported in more than 5% of Crysvita-treated adult XLH patients and in at least 2 patients more than placebo in one study are: back pain, headache, tooth infection, restless legs syndrome, vitamin D decreased, dizziness, constipation, muscle spasms, and blood phosphorus increased.
Spinal stenosis is prevalent in adults with XLH, and spinal cord compression has been reported. It is unknown if Crysvita therapy exacerbates spinal stenosis or spinal cord compression.
Adult TIO Patients

Adverse reactions reported in more than 10% of Crysvita-treated adult TIO patients in two studies are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.
USE IN SPECIFIC POPULATIONS

There are no available data on Crysvita use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Serum phosphorus levels should be monitored throughout pregnancy. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-888-756-8657.
There is no information regarding the presence of Crysvita in human milk or the effects of Crysvita on milk production or the breastfed infant.

On July 14, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported it entered into a clinical trial collaboration with Pharmacyclics, an AbbVie company, that includes supply of ibrutinib for its Phase 3 clinical trial (Press release, Oncternal Therapeutics, JUL 14, 2022, View Source [SID1234616682]).

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"This agreement represents a significant milestone for Oncternal as we advance towards the planned initiation of our registrational study ZILO-301 in the third quarter of 2022," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "Ibrutinib was the first Bruton’s tyrosine kinase (BTK) inhibitor in the market and its approval changed the treatment paradigm for patients suffering from certain hematological malignancies. We are pleased that this collaboration will support the development of an innovative combination of zilovertamab and ibrutinib that we believe may address important unmet needs of patients with MCL."

Under the terms of the collaboration, the supply of ibrutinib will support the company’s global registrational Phase 3 clinical trial of zilovertamab for the treatment of patients with relapsed or refractory mantle cell lymphoma (MCL), ZILO-301. The agreement also includes the supply of ibrutinib for Study ZILO-302, an open-label companion study of zilovertamab plus ibrutinib for patients who have progressive disease during the initial four months of ibrutinib monotherapy from Study ZILO-301.

About Zilovertamab (formerly Cirmtuzumab)
Zilovertamab is an investigational, humanized, potentially first-in-class monoclonal antibody targeting Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1). Zilovertamab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with MCL, chronic lymphocytic leukemia (CLL) or marginal zone lymphoma (MZL), in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, Oncternal is supporting two investigator-sponsored studies being conducted at the UC San Diego School of Medicine, a Phase 1b clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC), and a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, for patients with relapsed/refractory CLL. Both are open for enrollment.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen, not usually expressed on adult cells, but its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically inhibiting ROR1-expressing tumors. This led to the development of zilovertamab which binds this critical epitope of ROR1, highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when zilovertamab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to zilovertamab for the treatment of patients with MCL and CLL/small lymphocytic lymphoma. Zilovertamab is in clinical development and has not been approved by the FDA for any indication.

On July 14, 2022 NexImmune, Inc. (Nasdaq: NEXI), a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to orchestrate a targeted immune response by directing the function of antigen-specific T cells, reported that it has received IND clearance for the Company’s first cellular therapy product candidate addressing solid tumors (Press release, NexImmune, JUL 14, 2022, View Source [SID1234616681]). NEXI-003, an autologous antigen-specific T cell product (CD3+/CD4-), is being developed for patients with relapsed or refractory human papillomavirus (HPV)-related cancers.

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Kristi Jones, NexImmune’s CEO, commented, "The FDA clearance of our third IND marks another significant milestone for NexImmune and demonstrates our team’s continued focus and commitment to bringing novel therapies to patients with significant unmet need. NEXI-003 is our third T cell therapy and first candidate to in address solid tumors. NEXI-003 consists of T cell populations simultaneously directed against multiple HPV tumor-relevant antigen targets. The T cells in our product candidate will consist of T cell subtypes critical to both potential anti-tumor activity and a phenotype intended to produce long-term immunologic memory required for durable responses."

The Phase 1 trial will enroll patients at multiple clinical sites across the United States. The proposed study is a two-phase, multicenter, open-label, dose-finding, first-in-human (FIH) study to characterize the safety and clinical activity of NexImmune’s HPV tumor-relevant antigen-specific CD8+ T cell product candidate (NEXI-003) in patients with relapsed or refractory locally advanced or metastatic HPV-related oropharyngeal cancers (with confirmed histopathology detection of HPV-16 and/or HPV-18 expression), who have received at least 1 prior regimen of standard therapy according to local standard of care guidance(s). The dose escalation phase will consist of multiple safety cohorts investigating increasing doses of NEXI-003 followed by an expansion phase that will enroll 24 to 36 patients overall, depending on the number of dose escalations. All patients will be followed for at least one year. Following initial data and after the recommended Phase 2 dose has been confirmed, NexImmune plans to expand the NEXI-003 development program to include other HPV related malignancies and evaluate potential SOC combination options across the patient populations.

About HPV-Related Cancers

Human papillomavirus (HPV)-related cancers are common epithelial malignancies that account for approximately 5% of all cancers globally. These cancers cause an estimated 12,500 deaths each year in the United States and more than 300,000 deaths each year throughout the world. Histologically, this family of cancers consists of squamous cell carcinomas and adenocarcinomas that occur in various anatomical sites including the oropharynx, uterine cervix, anus, vagina, vulva and penis. The high-risk HPV subtypes are most commonly HPV-16 and HPV-18. Malignant transformation results through the activation of the expression of the E6 and E7 HPV oncogenes, which inhibit the tumor suppressors p53 and Rb. These oncoproteins also inhibit apoptosis of tumor cells, deregulate the cell cycle, result in the accumulation of genetic instability, promote angiogenesis and facilitate the invasiveness and metastatic spread of cancerous cells.

On July 14, 2022 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning ("ML") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that the Food and Drug Administration (FDA) has cleared the Company to proceed with its Phase 2 clinical trial, Harmonic, for its investigational new drug LP-300 (Press release, Lantern Pharma, JUL 14, 2022, View Source [SID1234616680]). The Harmonic trial will be a 90 patient, multi-center, two arm, open-label, and randomized clinical trial evaluating LP-300 in combination with chemotherapy for never smoker patients with advanced non-small cell lung cancer (NSCLC).

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"The launch of the Harmonic trial is a major milestone for LP-300. Our team is looking forward to beginning patient enrollment during the third quarter," said Panna Sharma, CEO and President of Lantern. "LP-300 is an innovative therapy that is being developed for never smokers with NSCLC, a unique and growing population of lung cancer patients whose cancer is genetically different from smokers with lung cancer. LP-300 will be delivered in combination with standard of care chemotherapy. Importantly, LP-300 has been well tolerated in prior clinical trials and has shown potential to protect against harmful effects of chemotherapy while also de-naturing many of the tyrosine kinase receptors through cysteine modification that are involved with NSCLC," continued Sharma.

About the Harmonic Trial and LP-300:

The Harmonic trial is a Phase 2 clinical trial that will assess the effect of Lantern’s investigational new drug LP-300 in combination with standard of care (SOC) chemotherapy, pemetrexed and carboplatin, on the overall and progression-free survival of never smoker patients with advanced NSCLC. The study has been designed as a 90 patient trial with approximately 2/3rds of the patients receiving LP-300 with chemotherapy and the remaining 1/3rd receiving chemotherapy alone. Lantern expects that initial patients will be enrolled into the Harmonic trial during the third quarter of 2022. Enrollment is expected to occur over the next 12 to 16 months across multiple sites in the US.

In a previous multi-center Phase 3 clinical trial, a subset of never smoker NSCLC patients who received LP-300 with chemotherapy showed increased overall and two-year survival of 91% and 125%, respectively, compared to patients who only received chemotherapy. In addition, LP-300 has been administered in multiple clinical trials to more than 1,000 people and has been generally well tolerated. LP-300 has also exhibited chemoprotective properties that may reduce side effects from chemotherapy. Additional information on the Harmonic trial can be found in the table below and at the link for the study’s registration and listing on the ClinicalTrials.gov website View Source

Protocol Title

A study of LP-300 with carboplatin and pemetrexed in never smokers with advanced lung adenocarcinoma (HARMONIC)

Study Design

90 patient, two arm study; approximately 60 patients will receive LP-300 with pemetrexed and carboplatin, approximately 30 patients will receive only pemetrexed and carboplatin.

Investigational Product

LP-300 in combination with pemetrexed and carboplatin

Summary of Key Eligibility Criteria

Adult never smoker patients with inoperable and advanced primary adenocarcinoma of the lung. Patients may have received prior treatment of tyrosine kinase inhibitors (TKIs).

Primary Outcome Measures

Progression free and overall survival

Secondary Outcome Measures

Objective response rate, duration of objective response, clinical benefit rate

About Lung Cancer in Never Smokers:

According to the American Cancer Society lung cancer is the second leading cause of cancer in the US. In 2021 there were an estimated 218,000 total patients diagnosed with lung cancer representing approximately a $11.5 billion market size. Historically, never smokers with NSCLC make up about 15-20% of all lung cancer patients, representing an approximate market size of $1.5 to 2.0 billion.

NSCLC presents differently in never smokers, which are defined by the CDC as a person who has smoked 100 cigarettes or less in their life, compared to smokers. These differences are believed due to a higher percentage of genetic mutations in a family of cancer-promoting genes called Tyrosine Kinases (TK). Changes in TK genes, such as EGFR, ALK, ROS and MET, can contribute to the development of healthy cells into cancer cells, leading to tumor formation and growth. LP-300’s intended mechanism is to work together with chemotherapy by strongly interacting in the TK gene pathways, interrupting their activity to slow or prevent tumor growth and spread.

On July 14, 2022 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the Company will host a conference call at 8:00 a.m. ET on Friday, July 29, 2022 to discuss its second quarter 2022 operating results (Press release, ImmunoGen, JUL 14, 2022, View Source [SID1234616679]). Management will also provide a brief update on the business.

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CONFERENCE CALL INFORMATION

To access the live call by phone, please register here. A dial-in and unique PIN will be provided to join the call. The call may also be accessed through the Investors and Media section of the Company’s website, www.immunogen.com. Following the call, a replay will be available at the same location.