On September 21, 2021 NanOlogy LLC, a clinical-stage interventional oncology drug company, reported that initial results from a Phase 1/2 clinical trial of intramural/intravesical (IMI/IVT) NanoDoce (large surface area microparticle [LSAM] docetaxel) suspension in high-risk nonmuscle invasive bladder cancer (hrNMIBC) were presented by Max Kates, MD (Johns Hopkins Medicine) at the American Urological Association annual meeting (AUA2021) via virtual platform on September 12, 2021 (Press release, NanOlogy, SEP 21, 2021, View Source;utm_medium=rss&utm_campaign=aus2021_presentation_highlights_pr [SID1234590065]).

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The oral presentation entitled Initial Results from a Phase 1/2 Trial of Large Surface Area Microparticle Docetaxel for High-Risk Non-Muscle Invasive Bladder highlighted safety and preliminary efficacy data from the multicenter dose-rising/confirmation clinical trial that enrolled 19 subjects. In addition to Dr. Kates, contributing clinical investigators were Ahmed Mansour, MD (UT Health San Antonio), Donald Lamm, MD (BCG Oncology), and Neal Shore, MD (Carolina Urologic Research Center).

Highlights from the presentation:

Overall, NanoDoce was well tolerated. Most treatment emergent adverse events were mild to moderate, and no severe adverse events were attributable to the study drug.
Systemic absorption of docetaxel was negligible and below the threshold for systemic toxicity in all subjects.
Across all doses and subjects (n=19), complete response (CR) at 3 months as 68% (13/19) and durability for responding subjects at 12 months was CR of 31% (4/13).
In the high-dose cohort (n=6), 6/6 maintained CR > 6 months with 4 subjects showing durability at 12 months, 1 subject showing recurrence, and 1 subject lost to follow up.
Tissue biopsies suitable for multiplexed immunofluorescence were obtained pre/post NanoDoce in 5 subjects. Analysis revealed directional increases in density of T Cells, macrophages (including PD-L1), and NK cells, and decreases in myeloid and MDSC cells.
NanoDoce (LSAM docetaxel) suspension is composed of large surface area microparticles of pure docetaxel designed for local administration and sustained drug release over time. In the dose-rising phase of the study (n=13), 3mg to 15mg of investigational drug were delivered IMI into and around the tumor resection bed post transurethral resection of bladder tumor (TURBT) followed by multiple periodic IVT of 50mg to 75mg. No dose limiting toxicities were encountered allowing target of 15mg IMI and 75mg IVT NanoDoce to continue into dose confirmation (n=6). Subjects were followed for up to one year. A separate study arm evaluated a post-TURBT single IMI/IVT administration of NanoDoce for safety over a 45-day period in 17 patients with muscle invasive bladder cancer. These data will be reported separately once final.

The American Cancer Society estimates 83,730 new cases of bladder cancer in the United States for 2021 with more than 20,000 presenting with hrNMIBC. For these patients, bladder removal often follows, which results in among the highest lifetime treatment costs and negative impact to quality of life of any cancer. NanOlogy is in planning of a later phase clinical trial in hrNMIBC.

In addition to this trial, NanOlogy clinical programs have advanced in lung, pancreatic, and other cancers. Data from preclinical and clinical studies in a variety of solid tumors have shown evidence of tumor kill, minimal local or systemic toxicity, and favorable antitumoral immune effects, which includes published preclinical research of NanoDoce synergy in combination with an immune checkpoint inhibitor.

The NanOlogy therapeutic platform is based on a proprietary supercritical precipitation technology that converts taxane API crystals into stable LSAMs of pure drug for tumor-directed therapy and sustained drug release. The taxane particles are covered by composition of matter patents issued in the US (US 9,814,685, US 10,507,195, & US 10,993,927), Canada, Europe, Japan, Russia, and Australia all valid through June 2036, plus applications pending globally. These composition of matter patents form the foundation of an extensive intellectual property portfolio protecting NanOlogy investigational drugs, methods, and technology.

On September 21, 2021 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported that the company will present at the 2021 Cantor Virtual Healthcare Conference on Tuesday, September 28, 2021 at 2:00 p.m. ET (Press release, BioCryst Pharmaceuticals, SEP 21, 2021, View Source [SID1234590064]).

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Links to a live audio webcast and replay of this presentation may be accessed in the Investors section of BioCryst’s website at http://www.biocryst.com.

On September 21, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported an update on its CD73 inhibitor program (Press release, ORIC Pharmaceuticals, SEP 21, 2021, View Source [SID1234590063]). ORIC recently announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug Application (IND) for ORIC-533 to proceed into a first-in-human clinical trial in which ORIC-533 will be tested as a single agent in an undisclosed tumor type not currently known to be under clinical evaluation with any other CD73 inhibitor. ORIC-533 was discovered internally at ORIC, is wholly owned, and is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens.

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In preclinical studies, ORIC-533 has demonstrated higher potency in a high AMP environment compared to all CD73 and adenosine receptor inhibitors against which it was compared, including both small molecules and antibodies, such as oleclumab. Preclinical data suggest ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of AMP levels observed in tumors.

Based on a preclinical collaboration with an academic key opinion leader that generated compelling single agent activity in patient derived model systems in an undisclosed tumor type, the company plans to pursue a single agent clinical development plan in this indication. ORIC expects to enroll its first patient in this trial during the fourth quarter of 2021. Also during the fourth quarter of 2021, ORIC plans to host an R&D event during which it will disclose the tumor indication along with the supporting preclinical rationale and data.

The second quarter ORIC-533 IND filing was the first of three planned IND/CTA filings by ORIC in 2021, with the IND filing for ORIC-944 (allosteric inhibitor of PRC2) and CTA filing for ORIC-114 (brain penetrant inhibitor of EGFR and HER2, including exon 20 insertion mutations) expected in the fourth quarter of 2021.

About ORIC-533

ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens. ORIC-533 has demonstrated greater potency in preclinical studies compared to an antibody approach, other small molecule CD73 inhibitors and inhibitors of adenosine receptors. Preclinical data suggest ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of AMP levels observed in tumors.

On September 21, 2021 Roivant Sciences Ltd. ("Roivant" or the "Company"), a next-generation biopharmaceutical company dedicated to improving the delivery of healthcare to patients, reported its financial results for the fiscal quarter ended June 30, 2021 and provided an update on the Company’s operations (Press release, Roivant Sciences, SEP 21, 2021, View Source [SID1234590062]).

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"Over the past quarter we have made significant progress as a business, both at Roivant centrally and across our family of companies," said Matthew Gline, Chief Executive Officer of Roivant. "I look forward to providing an update on these developments and an overview of key milestones to come at our R&D Day next week."

On September 28, Roivant will host its annual R&D Day, at which the Company will provide updates on clinical development at the Vants and Roivant’s new small molecule discovery engine. The webcast for this virtual event will begin at 1 p.m. ET and can be accessed at View Source

Recent Developments

Datavant: In June 2021, Datavant and Ciox Health entered into a definitive agreement to merge the two companies. The combined entity, named Datavant, is the nation’s largest health data ecosystem, enabling patients, providers, payers, health data analytics companies, patient-facing applications, government agencies and life science companies to securely exchange their patient-level data. The merger closed on July 27, 2021. At closing, Roivant received approximately $320 million in cash and a minority equity stake in the combined company.
Aruvant: In June 2021, Aruvant announced data published on ARU-2801, an investigational gene therapy, that showed improved survival out to 18 months in hypophosphatasia mice.
Immunovant: In August 2021, Roivant made a $200 million investment in Immunovant. Following this transaction, Roivant owns 73,398,664 shares of Immunovant common stock, representing approximately a 63.8% ownership interest.
Dermavant: In August 2021, the FDA accepted for filing Dermavant’s NDA for tapinarof for the treatment of plaque psoriasis in adult patients. The FDA has assigned a PDUFA target action date in the second calendar quarter of 2022. In September 2021, Dermavant dosed the first patient in a Phase 3 trial of tapinarof for the treatment of atopic dermatitis.
Genevant: In August 2021, Genevant entered into a global collaboration and license agreement with Takeda for the development and commercialization of novel nonviral gene therapies for up to two rare liver diseases. Genevant will be eligible for up to $303 million in upfront and potential milestone payments, plus royalties on product sales. This is the second collaboration between Genevant and Takeda.
Major Upcoming Milestones

Roivant: We expect to close our business combination with MAAC, along with a concurrent PIPE financing, and commence trading on Nasdaq on October 1 under the symbol "ROIV." Assuming no redemptions by MAAC shareholders, the business combination and concurrent PIPE financing are expected to deliver approximately $575 million in net proceeds to Roivant.
Dermavant: We expect a decision from the FDA on the approval of tapinarof for the treatment of adults with plaque psoriasis in the second calendar quarter of 2022. We also expect to report topline data from Dermavant’s Phase 3 clinical trial of tapinarof for the treatment of atopic dermatitis in the first half of calendar year 2023.
Immunovant: Contingent upon FDA feedback, Immunovant plans to initiate a pivotal trial evaluating IMVT-1401 for the treatment of myasthenia gravis in the early part of calendar year 2022. Immunovant also plans to announce at least two new indications and submit INDs with their trial designs to the FDA over the next 12 months.
Aruvant: We expect Aruvant to report additional clinical data from the ongoing Phase 1/2 trial of ARU-1801 in sickle cell disease patients in the second half of calendar year 2021.
First Fiscal Quarter 2021 Financial Summary

Research and Development Expenses

Research and development expenses increased by $19.9 million to $78.6 million for the three months ended June 30, 2021 compared to $58.7 million for the three months ended June 30, 2020. The increase is primarily due to an increase in personnel-related expenses, which is partially driven by additional headcount to support drug discovery efforts using our computational discovery technology and targeted protein degradation platform, following the acquisition of Silicon Therapeutics in March 2021 and Oncopia Therapeutics, Inc. in November 2020.

General and Administrative Expenses

General and administrative expenses increased by $25.6 million to $82.8 million for the three months ended June 30, 2021 compared to $57.1 million for the three months ended June 30, 2020. The increase was primarily due to increases in professional and transaction fees, personnel-related expenses and share-based compensation expense.

Capital Resources

As of June 30, 2021, we had cash and cash equivalents of approximately $2.0 billion.

On September 21, 2021 Eli Lilly and Company (NYSE: LLY) reported the pricing terms of its previously announced cash tender offer for specified series of its outstanding debt securities (Press release, Eli Lilly, SEP 21, 2021, View Source [SID1234590061]).

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Holders of notes subject to the tender offer who validly tendered, and did not validly withdraw, their notes on or before 5:00 p.m., New York City time, on September 20, 2021 (the early tender date), and whose notes are accepted for purchase by Lilly, are eligible to receive the applicable total consideration. The total consideration for each $1,000 principal amount of notes tendered and accepted for payment in the tender offer is based on the applicable reference yield plus a fixed spread, in each case as set forth in the table below, and is payable to holders of the notes listed in the table below who validly tendered and did not validly withdraw their notes on or before the early tender date and whose notes are accepted for purchase by Lilly. The reference yields listed in the table were calculated at 10:00 a.m., New York City time, on September 21, 2021. The applicable total consideration for each series of notes includes an early tender premium of $30 per $1,000 principal amount of notes validly tendered and not validly withdrawn and accepted for purchase by Lilly.

Title of Security

CUSIP No.

Acceptance
Priority
Level

Reference U.S. Treasury
Security

Reference
Yield

Fixed
Spread

Total
Consideration(1)(2)

4.150% Notes due 2059

532457 BU1

1(3)

2.375% due May 15, 2051

1.865%

80 bps

$1,347.88

3.950% Notes due 2049

532457 BT4

2(4)

2.375% due May 15, 2051

1.865%

70 bps

$1,268.49

7.125% Notes due 2025

532457 AM0

3

0.750% due August 31, 2026

0.820%

15 bps

$1,222.65

6.770% Notes due 2036

532457 AP3

4

1.250% due August 15, 2031

1.321%

105 bps

$1,530.04

5.950% Notes due 2037

532457 BC1

5

1.750% due August 15, 2041

1.816%

55 bps

$1,478.64

5.550% Notes due 2037

532457 BA5

6

1.750% due August 15, 2041

1.816%

50 bps

$1,418.71

5.500% Notes due 2027

532457 AZ1

7

0.750% due August 31, 2026

0.820%

40 bps

$1,226.23

4.650% Notes due 2044

532457 BG2

8

1.750% due August 15, 2041

1.816%

75 bps

$1,351.36

3.950% Notes due 2047

532457 BR8

9

2.375% due May 15, 2051

1.865%

70 bps

$1,255.48

3.875% Notes due 2039

532457 BS6

10

1.750% due August 15, 2041

1.816%

45 bps

$1,225.74

3.700% Notes due 2045

532457 BJ6

11

2.375% due May 15, 2051

1.865%

65 bps

$1,205.60

3.375% Notes due 2029

532457 BV9

12

1.250% due August 15, 2031

1.321%

15 bps

$1,130.16

3.100% Notes due 2027

532457 BP2

13

0.750% due August 31, 2026

0.820%

35 bps

$1,100.66

2.750% Notes due 2025

532457 BH0

14

0.750% due August 31, 2026

0.820%

0 bps

$1,065.36

2.350% Notes due 2022

532457 BQ0

15

1.750% due May 15, 2022

0.070%

10 bps

$1,014.09

(1) Per $1,000 principal amount of notes that are tendered and accepted for purchase.

(2) The applicable total consideration includes an early tender premium of $30 per $1,000 principal amount of notes that are tendered and accepted for purchase.

(3) Lilly has removed the previously announced note cap setting forth the maximum principal amount of 4.150% Notes due 2059 that Lilly will accept for purchase pursuant to the tender offer.

(4) Lilly has removed the previously announced note cap setting forth the maximum principal amount of 3.950% Notes due 2049 that Lilly will accept for purchase pursuant to the tender offer.

All payments for notes accepted for purchase in connection with the early tender date will also include accrued and unpaid interest on the principal amount of such notes to, but excluding, the initial settlement date, which is currently expected to be September 22, 2021.

Holders of notes subject to the tender offer who validly tender and do not validly withdraw their notes after the early tender date will, if such notes are accepted by Lilly, receive the applicable tender consideration, which is equal to the total consideration minus $30 per $1,000 principal amount of notes tendered by such holders and accepted for purchase by Lilly. Accrued and unpaid interest from the last interest payment date for the applicable series of notes to, but excluding, the applicable settlement date will be paid in cash in respect of all validly tendered notes accepted for purchase by Lilly in the tender offer.

The tender offer is scheduled to expire at 11:59 p.m., New York City time, on October 4, 2021, unless extended or terminated earlier.

In accordance with the terms of the tender offer, the withdrawal date was 5:00 p.m., New York City time, on September 20, 2021. As a result, tendered notes may no longer be withdrawn, except in certain limited circumstances where additional withdrawal rights are required by law.

The tender offer is being conducted on the terms and subject to the conditions set forth in the Offer to Purchase, dated September 7, 2021 (the "Offer to Purchase"), and the related Letter of Transmittal, each as supplemented by the press release, dated September 21, 2021, that removed the note caps for the 3.950% Notes due 2049 and the 4.150% Notes due 2059.

Lilly has retained BofA Securities, Inc. and Citigroup Global Markets Inc. to serve as lead dealer managers for the tender offer, and Barclays Capital, Inc., BNP Paribas Securities Corp. and Deutsche Bank Securities Inc. to serve as co-dealer managers. Lilly has retained Global Bondholder Services Corporation to serve as tender agent and information agent for the tender offer.

Requests for documents relating to the tender offer may be directed to Global Bondholder Services Corporation by telephone at +1 (866) 470-3900, by email at [email protected] or in writing at 65 Broadway, Suite 404, New York, NY 10006. Questions regarding the tender offer may be directed to BofA Securities, Inc. toll-free at +1 (888) 292-0070 or collect at +1 (980) 387-3907 or to Citigroup Global Markets Inc. toll-free at +1 (800) 558-3745 or collect +1 (212) 723-6106.

This press release is for informational purposes only and is not an offer to purchase, the solicitation of an offer to sell any notes. The tender offer is being made only pursuant to the Offer to Purchase and the information in this press release is qualified by reference to the Offer to Purchase. In any jurisdiction where the laws require the tender offer to be made by a licensed broker or dealer, the tender offer will be deemed made on behalf of Lilly by the dealer managers, or one or more registered brokers or dealers under the laws of such jurisdiction. None of Lilly or its affiliates, their respective boards of directors, the Dealer Managers, Global Bondholder Services Corporation or the trustee with respect to any series of notes is making any recommendation as to whether holders should tender any notes in response to the tender offer, and neither Lilly nor any such other person has authorized any person to make any such recommendation. Holders must make their own decision as to whether to tender any of their notes, and, if so, the principal amount of notes to tender.

In addition, this press release is not an offer to sell or the solicitation of an offer to buy any securities. No offer, solicitation, purchase or sale will be made in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. Any such securities will be offered only by means of a prospectus, including a prospectus supplement relating to such securities, meeting the requirements of Section 10 of the Securities Act of 1933, as amended.