vTv Therapeutics to Present at the 30th Annual Piper Jaffray Healthcare Conference

On November 19, 2018 vTv Therapeutics Inc. (Nasdaq: VTVT) reported that company management will present a corporate overview at the Piper Jaffray 30th Annual Healthcare Conference on Tuesday, Nov. 27, 2018 at 2:10 p.m. ET in New York City (Press release, vTv Therapeutics, NOV 19, 2018, View Source;p=irol-newsArticle&ID=2377689 [SID1234531441]).

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A live webcast of the presentation can be accessed here and will be archived for 30 days following the presentation at www.vtvtherapeutics.com.

vTv Therapeutics is a clinical-stage biopharmaceutical company engaged in the discovery and development of orally administered small molecule drug candidates to fill significant unmet medical needs. vTv has a pipeline of clinical drug candidates led by programs for the treatment of Alzheimer’s disease and diabetes as well as treatment of inflammatory disorders.

Agilent Technologies Reports Fourth-Quarter Fiscal Year 2018 Financial Results

On November 19, 2018 Agilent Technologies, Inc. (NYSE: A) reported revenue of $1.29 billion for the fourth-quarter ended October 31, 2018, up 9 percent year over year (up 9 percent on a core basis(1)) (Press release, Agilent, NOV 19, 2018, http://www.agilent.com/about/newsroom/presrel/2018/19nov-gp18063.html [SID1234531466]).

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Fourth-quarter GAAP net income was $195 million, or $0.61 per share. Last year’s fourth-quarter GAAP net income was $177 million, or $0.54 per share.

"The Agilent team delivered an outstanding quarter to wrap up the fiscal year with revenues and earnings per share ahead of expectations," said Mike McMullen, Agilent CEO and President. "Our performance this quarter caps off an excellent 2018 as we achieved our highest annual core growth rate and profitability since becoming a stand-alone life sciences company in 2014."

"During the quarter we continued our investment in growth introducing new and differentiated products and services," continued McMullen. "We leveraged our strong balance sheet completing several acquisitions to further strengthen our portfolio. We also returned over $600 million to shareholders through stock buybacks and dividends this year.

"We enter fiscal 2019 with momentum. Our focus remains on executing our shareholder value creation model to deliver superior earnings growth."

Financial Highlights

Life Sciences and Applied Markets Group

Fourth-quarter revenue of $597 million from Agilent’s Life Sciences and Applied Markets Group (LSAG) grew 8 percent year over year (up 9 percent on a core basis(1)), with broad-based strength across major end markets, platforms and regions. LSAG’s operating margin for the quarter was 25.9 percent. Full-year revenue of $2.3 billion grew 9 percent year over year (up 7 percent on a core basis(1)). LSAG’s operating margin for the year was 24.1 percent.

Agilent CrossLab Group

Fourth-quarter revenue of $441 million from Agilent CrossLab Group (ACG) grew 9 percent year over year (up 9 percent on a core basis(1)). Demand was excellent across both services and consumables. ACG’s operating margin for the quarter was 24.7 percent. Full-year revenue of $1.7 billion grew 11 percent year over year (up 8 percent on a core basis(1)). ACG’s operating margin for the year was 23.3 percent.

Diagnostics and Genomics Group

Fourth-quarter revenue of $256 million from Agilent’s Diagnostics and Genomics Group (DGG) grew 9 percent year over year (up 5 percent on a core basis(1)) led by pharma growth and strong demand for genomics and NASD products. DGG’s operating margin for the quarter was 23.3 percent. Full-year revenue of $943 million grew 10 percent year over year (up 5 percent on a core basis(1)). DGG’s operating margin for the year was 18.9 percent.

2019 First Quarter and Full Year Outlook

For fiscal year 2019, Agilent expects revenue of $5.13 billion to $5.17 billion, representing growth of 4.4 to 5.2 percent and core growth of 5.0 to 5.5 percent(1). Full-year 2019 non-GAAP earnings of $3.00 to $3.05 per share(3). The guidance is based on October 31, 2018 currency exchange rates.

Agilent expects first-quarter 2019 revenue in the range of $1.265 billion to $1.280 billion, representing growth of 4.4 to 5.7 percent and core revenue growth of 4.5 to 5.5 percent(1). First-quarter 2019 non-GAAP earnings are expected to be in the range of $0.71 to $0.73 per share(3).

New Share Repurchase Program

Agilent’s Board of Directors approved a new share repurchase program authorizing the purchase of up to $1.75 billion of common stock. The 2018 share repurchase program commences on November 21, 2018, replacing the previous program.

The number of shares to be repurchased and the timing of any repurchases will depend on factors such as the share price, economic and market conditions, and corporate and regulatory requirements. The share repurchase program may be suspended, amended or discontinued at any time.

Conference Call

Agilent’s management will present more details about its fourth-quarter FY2018 financial results on a conference call with investors today at 1:30 p.m. (Pacific Time). This event will be webcast live in listen-only mode. Listeners may log on at www.investor.agilent.com and select "Q4 2018 Agilent Technologies Inc. Earnings Conference Call" in the "News & Events Calendar of Events" section. The webcast will remain available on the company’s website for 90 days.

Additional information regarding financial results can be found at www.investor.agilent.com by selecting "Financial Results" in the "Financial Information" section.

In addition, a telephone replay of the conference call will be available at approximately November 19, 2018 at 4:30 p.m. (Pacific Time) after the call and through November 26 by dialing +1 855-859-2056 (or +1 404-537-3406 from outside the United States) and entering pass code 6519506.

The adjustment for taxes excludes tax benefits that management believes are not directly related to on-going operations and which are either isolated or cannot be expected to occur again with any regularity or predictability. For the three months and year ended October 31, 2018 and 2017, management uses a non-GAAP effective tax rate of 18.0%.

We provide non-GAAP net income and non-GAAP net income per share amounts in order to provide meaningful supplemental information regarding our operational performance and our prospects for the future. These supplemental measures exclude, among other things, charges related to asset impairments, amortization of intangibles, business exit and divestiture costs, transformational initiatives, acquisition and integration costs, pension settlement gain, gain on step acquisition of Lasergen, NASD site costs, special compliance costs, and adjustment for Tax Reform.

Asset impairments include assets that have been written down to their fair value.

Business exit and divestiture costs include costs associated with business divestitures.

Transformational initiatives include expenses associated with targeted cost reduction activities such as manufacturing transfers including costs to move manufacturing due to new tariffs and tariff remediation actions, small site consolidations, legal entity and other business reorganizations, insourcing or outsourcing of activities. Such costs may include move and relocation costs, one-time termination benefits and other one-time reorganization costs. Included in this category are also expenses associated with company programs to transform our product lifecycle management (PLM) system, human resources and financial systems.

Acquisition and Integration costs include all incremental expenses incurred to effect a business combination. Such acquisition costs may include advisory, legal, accounting, valuation, and other professional or consulting fees. Such integration costs may include expenses directly related to integration of business and facility operations, the transfer of assets and intellectual property, information technology systems and infrastructure and other employee-related costs.

Pension settlement gain resulted from transfer of the substitutional portion of our Japanese pension plan to the government.

Gain on step acquisition of Lasergen resulted from the measurement at fair value of our equity interest held at the date of business combination.

NASD site costs include all the costs related to the expansion of our manufacturing of nucleic acid active pharmaceutical ingredients incurred prior to the commencement of commercial manufacturing.

Special compliance costs include costs associated with transforming our processes to implement new regulations such as the EU’s General Data Protection Regulation (GDPR), revenue recognition and certain tax reporting requirements.

Other includes certain legal costs and settlements in addition to other miscellaneous adjustments.

Adjustment for Tax Reform primarily consists of an estimated provision of $499 million for U.S. transition tax and correlative items on deemed repatriated earnings of non-U.S. subsidiaries and an estimated provision of $53 million associated with the decrease in the U.S. corporate tax rate from 35% to 21% and its impact on our U.S. deferred tax assets and liabilities. The taxes payable associated with the transition tax, net of tax attributes, on deemed repatriation of foreign earnings is approximately $426 million, payable over 8 years.

Our management uses non-GAAP measures to evaluate the performance of our core businesses, to estimate future core performance and to compensate employees. Since management finds this measure to be useful, we believe that our investors benefit from seeing our results "through the eyes" of management in addition to seeing our GAAP results. This information facilitates our management’s internal comparisons to our historical operating results as well as to the operating results of our competitors.

Our management recognizes that items such as amortization of intangibles can have a material impact on our cash flows and/or our net income. Our GAAP financial statements including our statement of cash flows portray those effects. Although we believe it is useful for investors to see core performance free of special items, investors should understand that the excluded items are actual expenses that may impact the cash available to us for other uses. To gain a complete picture of all effects on the company’s profit and loss from any and all events, management does (and investors should) rely upon the GAAP income statement. The non-GAAP numbers focus instead upon the core business of the company, which is only a subset, albeit a critical one, of the company’s performance.

Readers are reminded that non-GAAP numbers are merely a supplement to, and not a replacement for, GAAP financial measures. They should be read in conjunction with the GAAP financial measures. It should be noted as well that our non-GAAP information may be different from the non-GAAP information provided by other companies.

The preliminary non-GAAP net income and diluted EPS reconciliation is estimated based on our current information.

Income from operations reflect the results of our reportable segments under Agilent’s management reporting system which are not necessarily in conformity with GAAP financial measures. Income from operations of our reporting segments exclude, among other things, charges related to asset impairments, amortization of intangibles, business exit and divestiture costs, transformational initiatives, acquisition and integration costs, pension settlement gain, gain on step acquisition of Lasergen, NASD site costs, and special compliance costs.

Readers are reminded that non-GAAP numbers are merely a supplement to, and not a replacement for, GAAP financial measures. They should be read in conjunction with the GAAP financial measures. It should be noted as well that our non-GAAP information may be different from the non-GAAP information provided by other companies.

We compare the year-over-year change in revenue excluding the effect of recent acquisitions and divestitures and foreign currency rate fluctuations to assess the performance of our underlying business.

(a) The constant currency year-over-year growth percentage is calculated by recalculating all periods in the comparison period at the foreign currency exchange rates used for accounting during the last month of the current quarter, and then using those revised values to calculate the year-over-year percentage change.

(b) The dollar impact from the current quarter currency impact is equal to the total year-over-year dollar change less the constant currency year-over-year change.

The preliminary reconciliation of GAAP revenue adjusted for recent acquisitions and divestitures and impact of currency is estimated based on our current information.

We compare the year-over-year change in revenue excluding the effect of recent acquisitions and divestitures and foreign currency rate fluctuations to assess the performance of our underlying business.

(a) The constant currency year-over-year growth percentage is calculated by recalculating all periods in the comparison period at the foreign currency exchange rates used for accounting during the last month of the current quarter, and then using those revised values to calculate the year-over-year percentage change.

(b) The dollar impact from the current year currency impact is equal to the total year-over-year dollar change less the constant currency year-over-year change.

The preliminary reconciliation of GAAP revenue adjusted for recent acquisitions and divestitures and impact of currency is estimated based on our current information.

Novartis receives positive CHMP opinion to expand Kisqali® combination therapy to all women with HR+/HER2- locally advanced or metastatic breast cancer

On November 16, 2018 Novartis reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an expanded indication for Kisqali (ribociclib), the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent, superior and sustained efficacy compared to endocrine therapy alone (Press release, Novartis, NOV 16, 2018, View Source [SID1234531397]). CHMP recommended Kisqali for the treatment of women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer in combination with fulvestrant as initial endocrine-based therapy and in women who have received prior endocrine therapy. The positive opinion also recommended approval of Kisqali in combination with endocrine therapy and a luteinising hormone-release hormone agonist (LHRH) for pre- and perimenopausal women.

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"Today’s CHMP opinion brings us one step closer to providing more women with HR+/HER2- advanced breast cancer in Europe with a treatment option," said Liz Barrett, CEO, Novartis Oncology. "The MONALEESA Phase III program enrolled more than 2,000 women, giving Kisqali by far the most extensive first-line evidence in clinical trials among any of the CDK4/6 inhibitors. This is another testament to how we are reimagining cancer."

This positive CHMP opinion is based on data from the Phase III MONALEESA-7 and MONALEESA-3 trials. These trials demonstrated prolonged progression-free survival (PFS) for Kisqali-based regimens compared to endocrine therapy alone and showed improvements as early as eight weeks after start of treatment with Kisqali combination therapy.

In MONALEESA-7, Kisqali plus an aromatase inhibitor and goserelin nearly doubled the median PFS compared to an aromatase inhibitor and goserelin alone in pre- or perimenopausal women (27.5 months compared to 13.8 months; HR=0.569; 95% CI: 0.436-0.743)[3]. In MONALEESA-3, Kisqali plus fulvestrant demonstrated a median PFS of 20.5 months compared to 12.8 months for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732) across the overall population of first-line and second-line postmenopausal women[4]. Across the two trials, the most common adverse reactions (incidence >=20%) were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough[3],[4].

Globally, an estimated 267,000 women will be diagnosed with advanced breast cancer each year and up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease[5],[6]. One in five women diagnosed with breast cancer in Europe are younger than 50 years old[7]. Premenopausal breast cancer is a biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer death in women 20-59 years old[1],[8]. These young women face specific challenges, including induction of premature menopause, emotional distress and strain on their professional and personal lives[9],[10],[11].

The European Commission will review the CHMP recommendation and usually delivers its final decision within two months. The decision will be applicable to all 28 European Union member states plus Iceland, Norway and Liechtenstein. Additional regulatory filings are underway with other health authorities worldwide.

About Kisqali (ribociclib)
Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably[1].

Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial[12]. In July 2018, Kisqali was approved by the FDA for the treatment of pre-, peri- or postmenopausal women in the US, and indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women[1].

Kisqali is approved for use in more than 70 countries around the world, including the United States and European Union member states. Kisqali is not currently approved for use in combination with fulvestrant or in premenopausal women in Europe. Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals[12].

About Novartis in Advanced Breast Cancer
For more than 30 years, Novartis has been tackling breast cancer with superior science, great collaboration and a passion for transforming patient care. With one of the most diverse breast cancer pipelines and one of the largest numbers of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.

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.

Janssen receives positive CHMP opinion for ERLEADA™ (apalutamide) for patients with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease

On November 16, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) reported it has issued a positive opinion for apalutamide, a next generation oral androgen receptor inhibitor for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.2 The CHMP’s positive opinion will now be reviewed by the European Commission (EC), which has the authority to grant approval for the use of apalutamide (Press release, Johnson & Johnson, NOV 16, 2018, View Source [SID1234531398]).

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The CHMP’s positive opinion is based on data from the pivotal SPARTAN Phase 3 clinical study which assessed the safety and efficacy of apalutamide versus placebo in patients with nmCRPC who have a rapidly rising prostate specific antigen (PSA) level despite receiving continuous androgen deprivation therapy (ADT). The SPARTAN clinical study showed that apalutamide, when added to ADT, significantly reduced the risk of developing distant metastasis or death (metastasis free survival [MFS]) by 72 percent, compared to placebo in combination with ADT (HR = 0.28; 95% CI, 0.23-0.35; P < 0.001). The median MFS was improved by over two years (40.5 months vs 16.2 months) in patients with nmCRPC whose PSA is rapidly rising.1 This study was published in The New England Journal of Medicine.

The most common Grade 3/4 treatment-emergent adverse events in the SPARTAN study were hypertension (14.3 percent vs. 11.8 percent), rash (5.2 percent vs. 0.3 percent), fall (1.7 percent vs. 0.8 percent) and fracture (2.7 percent vs. 0.8 percent). Treatment discontinuation due to adverse events was 11 percent in the apalutamide arm compared to 7 percent in the placebo arm. Rates of serious adverse events were similar in the apalutamide in combination with ADT arm versus placebo in combination with ADT arm (25 percent vs. 23 percent respectively).1

"Data from the SPARTAN study showed that apalutamide significantly improves metastasis free survival for patients with castration-resistant prostate cancer," said Dr Simon Chowdhury, Consultant Medical Oncologist, Guy’s and St Thomas’ Hospitals. "Nearly 90 percent of patients with castration-resistant prostate cancer will eventually develop bone metastases. At that point their prognosis worsens dramatically. Delaying the spread of cancer is therefore critical for patients living with prostate cancer."*

"We are pleased with the CHMP’s decision to recommend approval of apalutamide for the treatment of patients with high-risk non-metastatic castration-resistant prostate cancer," said Dr. Ivo Winiger-Candolfi M.D., Janssen Oncology Solid Tumor Therapy Area Lead, Europe, Middle East and Africa, Cilag GmbH International. "We know that each prostate cancer patient journey is unique and today’s positive CHMP opinion brings us one step closer to offering patients an effective treatment option that delays the spread of their disease."

ENDS

About Non-Metastatic Castration-Resistant Prostate Cancer

Non-metastatic castration-resistant prostate cancer (CRPC) refers to a disease stage when the cancer no longer responds to medical or surgical treatments that lower testosterone, but has not yet been discovered in other parts of the body using a bone scan or CT scan.3 Features include: lack of detectable metastatic disease; rapidly rising prostate-specific antigen while on androgen deprivation therapy (ADT) and serum testosterone level below 50 ng/dL.3 Ninety percent of patients with non-metastatic CRPC will eventually develop bone metastases, which can lead to pain, fractures and spinal cord compression.4 The relative 5-year survival rate for patients with distant stage castration sensitive or castration resistant prostate cancer is 30 percent.5,6

About apalutamide

Apalutamide is an investigational, next-generation oral androgen receptor (AR) inhibitor that blocks the androgen signaling pathway in prostate cancer cells. Apalutamide inhibits the growth of cancer cells in three ways: by preventing the binding of androgen to the AR; by stopping the AR from entering the cancer cells; and by preventing the AR from binding to the DNA of the cancer cell.7

Janssen submitted a Marketing Authorisation Application to the European Medicines Agency (EMA) in February 2018 seeking approval for apalutamide for the treatment of patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Apalutamide received approval from the United States Food and Drug Administration for the treatment of patients with nmCRPC in February 2018, shortly followed by approvals in Canada, Australia, Argentina and Brazil.8,9,10,11

First-in-Human Trial Launched for Super-Enhancer Inhibitor GZ17-6.02

On November 16, 2018 Genzada Pharmaceuticals USA Inc., a subsidiary of Ionics Life Sciences Limited (Genzada), reported that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for a Phase 1 human clinical trial of the company’s flagship molecule GZ17-6.02 (6.02) for patients with advanced solid organ tumors or lymphoma (Press release, Genzada Pharmaceuticals, NOV 16, 2018, View Source [SID1234531399]).

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"We are excited to bring 6.02 to the oncology community and we look forward to demonstrating its safety and efficacy as we move through the clinical trials process," said Cameron E. West, MD, FAAD, chief operating officer of Genzada. "Based on numerous preclinical studies, we believe this therapeutic will be very well-tolerated and will achieve meaningful outcomes for cancer patients."

6.02 has shown preclinical success in several therapeutic contexts, notably for pancreatic cancer and head and neck squamous cell carcinoma.

"It is great news that the IND clearance has been granted for 6.02," said Daniel D. Von Hoff, MD, chief development officer at TD2 and adviser to Genzada. TD2 supported the research sponsor with its regulatory submissions, including the completion and filing of the drug’s IND application. The clinical research organization (CRO) will continue to manage the clinical trial for 6.02. "I know how hard the team has worked to get to this milestone for this very interesting combination with a unique mechanism of action."

Functionally, the compound acts as an inhibitor to super-enhancers, the areas of the genome bound by transcription factors that are uniquely susceptible to repair signal disruption. 6.02 can inhibit several super-enhancer targets based on the cancer of origin.

GZ17-6.02 is derived in part from Arum palaestinum (black calla lily), a native plant found in several regions of the Middle East. Similar to the vinca alkaloids and taxanes, 6.02 is now a fully synthesized therapeutic, originally derived from naturally occurring compounds.

Enrollment of the first patient for the 6.02 trial will take place through the HonorHealth Research Institute, and will be announced in the coming months as the study initiates.