On May 8, 2021 Daiichi Sankyo and partner AstraZeneca reported that next-gen antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) has show glimmers of efficacy and a reasonable safety profile in its first data release in breast cancer (Press release, AstraZeneca, MAY 8, 2021, https://www.fiercebiotech.com/biotech/daiichi-sankyo-astrazeneca-s-5b-enhertu-follow-up-shows-early-signs-success-breast-cancer [SID1234579494]).

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Having already seen some positives in its non-small cell lung cancer test, which is further along, Daiichi and AstraZeneca published the first look at Dato-DXd in triple-negative breast cancer (TNBC) at a late-breaking mini oral presentation at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Virtual Congress conference Saturday.

Nearly one year ago, AZ agreed to pay $1 billion upfront over two years for ex-Japan rights to the drug, which works as an ADC that targets tumor-associated protein TROP2, plus another $5 billion in milestones.

The drug combines an antibody targeting TROP2 that’s conjugated using a stable linker with a potent topoisomerase I inhibitor payload. It has a lower drug-to-antibody ratio that Daiichi suggests should both boost cell-killing activity and limit side effects.

The deal for the drug was after the success of AZ’s $6.9 billion deal for Enhertu (trastuzumab deruxtecan) from Daiichi, penned back in 2019. Within a few months of AZ coming on board, that drug was approved for patients with previously treated HER2-positive breast and gastric cancer. Dato-DXd will not be matching that record, but its TNBC data out over the weekend have the Japanese pharma optimistic about its future.

The data are still early, just a phase 1 and in only 21 patients, and Daiichi was keen to stress that there is a far way to go show just how well its drug workscu and how safe it will be in a larger patient population.

But in an early peek, the TNBC cohort of the TROPION-PanTumor01 phase 1 trial saw an objective response rate, assessed by blinded independent central review, hit 43% in 21 evaluable patients treated with Dato-DXd.

Five confirmed complete or partial responses were also seen, with four additional CR/PRs awaiting confirmation at the time of data cutoff on Jan. 8, 2021. A disease control rate of 95% was also observed.

RELATED: Gilead splashes out $21B for Immmunomedics, keeping the pedal on new target weeks after AZ-Daiichi deal

No p-values have yet been assigned, but this favors well (with the many cross-trial comparison caveats abound) with what will likely be its main rival, Gilead/Immunomedics’ Trodelvy (sacituzumab govitecan-hziy), an antibody and topoisomerase inhibitor conjugate directed to the TROP-2 receptor, which has, among others, FDA approval in TNBC that has spread.

At ESMO (Free ESMO Whitepaper) 2020, Trodelvy showed an ORR of 35%, though this was a phase 3 with more patients, and it also saw overall survival with a median of 12.1 months versus 6.7 months for chemo. Future trials for Daiichi’s drug will look to assess its survival potential, a key weapon it will need for any approval, but the company saw reasons to be cheerful about its prospects from these data.

On the safety side there had been concerns about drug-related interstitial lung disease, which had been noted by analysts as being seen in earlier trials. Daiichi said no such ILD cases were seen in this test, though Gilles Gallant, Ph.D., senior vice president and global head, oncology development, oncology R&D at Daiichi, told Fierce Biotech that they could not say for sure that this was not an issue, and future trials are needed to find that answer.

It did see less instances of severe diarrhea than are usual with the tech it uses, though six patients did have to have dose reductions because of adverse events. Daiichi said that these were most commonly due to stomatitis (13%) and mucosal inflammation (8%). Grade 3 or higher treatment emergent adverse events, regardless of cause, occurred in 33% of patients. The most common adverse events overall were stomatitis, nausea, fatigue, vomiting, and alopecia. No-one left the test due to adverse events, however.

Gallant, who was cautious about the trial simply because of how early it is and the small number of patients, does believe the drug is best-in-class in terms of its construct which differs from the likes of Trodelvy.

On May 8, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca reported that New data from datopotamab deruxtecan (Dato-DXd), a TROP2 directed DXd antibody drug conjugate (ADC), showed preliminary response and disease control in patients with metastatic triple negative breast cancer (TNBC) with disease progression following standard treatment (Press release, Daiichi Sankyo, MAY 8, 2021, View Source [SID1234579499]).

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These preliminary data from the TNBC cohort of the TROPION-PanTumor01 phase 1 study were presented as a late-breaking mini oral presentation (Abstract #LBA4) at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Virtual Congress (#ESMOBreast21).

TNBC accounts for approximately 10 to 15% of breast cancer cases and is associated with higher disease recurrence and worse prognosis compared to other breast cancer subtypes.1,2,3 It is estimated that only 12.2% of patients with metastatic TNBC survive five years and median overall survival is generally less than two years.2,3

The preliminary objective response rate (ORR), assessed by blinded independent central review, was 43% in 21 evaluable patients treated with datopotamab deruxtecan [6 mg/kg (n=19) or 8 mg/kg (n=2)]. Five confirmed complete or partial responses (CR/PRs) were seen, with four additional CR/PRs awaiting confirmation at the time of data cut-off of January 8, 2021. A disease control rate of 95% was observed.

"There are currently limited treatment options for patients with previously treated metastatic triple negative breast cancer, historically a very difficult-to-treat subtype of breast cancer," said Aditya Bardia, MD, MPH, Director of Breast Cancer Research, Mass General Cancer Center, Harvard Medical School. "These initial safety and efficacy results of datopotamab deruxtecan in patients with triple negative breast cancer are encouraging and warrant further development for patients with breast cancer."

The safety profile of datopotamab deruxtecan seen in the TNBC cohort is consistent with safety that has been previously reported in the non-small cell lung cancer (NSCLC) cohort of TROPION-PanTumor01. No patients discontinued treatment due to adverse events (AEs); however, dose reductions due to AEs occurred in six patients (25%) and were most commonly due to stomatitis (13%) and mucosal inflammation (8%). Grade 3 or higher treatment emergent adverse events (TEAEs) regardless of causality occurred in 33% of patients. TEAEs grade 3 or higher included stomatitis (13%), fatigue (4%) and anemia (4%) with no grade 3 or higher TEAEs of diarrhea or neutropenia. The most common TEAEs overall in ≥25% of patients were stomatitis, nausea, fatigue, vomiting, and alopecia. No cases adjudicated as drug-related interstitial lung disease (ILD) were observed.

"These preliminary results provide proof-of-concept that targeting TROP2 with datopotamab deruxtecan may be an effective treatment strategy for patients with previously treated metastatic triple negative breast cancer," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "We are encouraged by the early tumor responses and disease control seen in these patients and we will continue to explore the potential of datopotamab deruxtecan in several types of breast cancer, including triple negative breast cancer."

"Triple negative breast cancer is known to be particularly aggressive and fast growing, and after treatment the risk of recurrence is faster and higher than in any other breast cancer subgroup," said Cristian Massacesi, Senior Vice President, Head of Late Stage Development Oncology R&D, AstraZeneca. "The preliminary results for datopotamab deruxtecan in this cohort of pretreated patients are encouraging for this high-potential targeted ADC."

Patients were treated with a median of four prior lines of therapy (range, 1-9, including prior lines of therapy in the [neo]adjuvant or metastatic setting) with a majority (88%) receiving more than two previous lines of treatment, including a taxane (83%), platinum-based chemotherapy (50%), immunotherapy (33%), sacituzumab govitecan (8%) and a PARP inhibitor (4%). As of data cut-off on January 8, 2021, 75% of patients remained on treatment with datopotamab deruxtecan.

Summary of TROPION-PanTumor01 Results

Efficacy Measure

Total Evaluable in TNBC Cohort (N=21)i, ii

ORR, %iii, iv

43% (n=9)

CR/PR (confirmed)

n=5

CR/PR (pending confirmation)

n=4

DCR, %v

95% (n=20)

PD, %

5% (n=1)

CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response

i Includes response evaluable patients who had ≥1 postbaseline tumor assessment or discontinued treatment. Postbaseline tumor assessments were not yet available for 3 patients at the data cutoff. One patient was not confirmed to have a target lesion per BICR and therefore had a best overall response of non-CR/non-PD.

ii Includes 2 patients that received 8 mg/kg datopotamab deruxtecan prior to selection of the 6-mg/kg dose for dose expansion.

iii Includes patients with a best overall response of CR, PR, stable disease, or non-CR/non-PD.

iv ORR is CR+PR; Responses are confirmed (CRs/PRs; n=5) plus those ongoing CRs/PRs too early to be confirmed (n=4).

v DCR is CR+PR+SD.

About TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicenter phase 1 trial designed to evaluate the safety, tolerability and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumors refractory to or relapsed from standard treatment or for whom no standard treatment is available, including NSCLC, TNBC and hormone receptor positive (HR+) breast cancer.

The dose escalation part of the study assessed the safety and tolerability of increasing doses of datopotamab deruxtecan to determine the maximum tolerated dose and/or recommended dose for expansion in patients with unresectable advanced NSCLC. The dose expansion part of the study further assessed the safety and tolerability of datopotamab deruxtecan at selected dose levels (4 mg/kg, 6 mg/kg and 8 mg/kg) in patients with NSCLC. Based on the preliminary efficacy and safety, the 6 mg/kg dose has been identified as the recommended dose for the NSCLC cohort.

The TNBC cohort was added in July 2020 and is currently evaluating patients with metastatic TNBC receiving datopotamab deruxtecan (6 mg/kg) with disease relapse or progression with standard treatment. The HR positive/HER2 negative cohort was added in March 2021 and is currently evaluating patients with metastatic HR positive/HER2 negative breast cancer receiving datopotamab deruxtecan (6 mg/kg) with disease relapse or progression with standard treatment.

Safety endpoints include dose limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DCR, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.

About TROP2 in Triple Negative Breast Cancer
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is overexpressed in several types of solid tumors, including breast cancer.4 Research indicates that high TROP2 expression is associated with cancer cell growth and proliferation and poor patient survival.4,5 While TROP2 is expressed across all breast cancer subtypes, it is overexpressed in approximately 80% of patients with TNBC, making it a promising molecular target for therapeutic development.5

Approximately 10 to 15% of patients with breast cancer are considered triple negative because the tumors test negative for estrogen, progesterone hormone receptors (HRs) and human epidermal growth factor 2 receptor (HER2).1,2,6 An estimated 260,000 new cases of TNBC were reported globally in 2018 with it being more common in younger women and those who are Black.1,2,7 Compared to patients with other breast cancer subtypes, prognosis for patients with metastatic TNBC is generally worse and the disease is more likely to recur following treatment with initial chemotherapy.1,3 Five-year survival of metastatic TNBC is estimated at 12.2% and median overall survival is generally less than two years.2,3

About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is a TROP2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform.

A comprehensive development program called TROPION is underway globally with trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple solid tumors, including NSCLC, TNBC and HR+ breast cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.

On May 7, 2021 Radius Health, Inc. ("Radius" or the "Company") (Nasdaq: RDUS), reported its financial results for the first quarter ended March 31, 2021 (Press release, Radius, MAY 7, 2021, View Source [SID1234579464]).

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The following are key components of Q1, 2021 performance:

Q1, 2021 FINANCIAL HIGHLIGHTS:

Total net revenue improved by 17% year-over-year: $56 million in 2021 vs. $48 million in 2020
TYMLOS U.S. product net revenue down 6% year-over-year: $45 million in 2021 vs. $48 million in 2020
Reduced unit volumes from inventory channel destocking plus volatility in patient activity as a result of Covid-19 during 2020; there was a partial offset from an increase in net price
TYMLOS U.S. new patient adds grew by 14% in Q1, 2021 vs. Q4, 2020
Strong cash balance: $115 million of cash, cash equivalents and marketable securities as of 3/31/2021
Strategic and proactive management of capital structure:
Completed $175 million financing transaction in March, 2021
Redeemed ~37% of aggregate principal amount of the existing 3.00% convertible notes
Eliminated potential future dilution by ~2 million shares (~4.9% of outstanding shares)
Improved financial flexibility with a more balanced mix of secured and unsecured tranches
Added cash to the balance sheet to enhance liquidity
BUSINESS HIGHLIGHTS:

Abaloparatide:

On May 1, 2021, Humana added TYMLOS to the formularies of its Medicare Advantage Plans
Impact #1: adds ~5 million beneficiaries, which moves Medicare Part D coverage from 83% to 91%
Impact #2: increases coverage for first line PMO patients with history of fracture from 77% to 78%
Q1 TYMLOS new patient prescribers: 42 of top 50 HCP’s are now orthopedic or specialist bone practices
New patient growth for this group (the 42) was 26% vs. 14% for total Q1 TYMLOS prescriber activity
Re-submission of abaloparatide to the EMA targeted to occur in Q4, 2021
TYMLOS Black Box Warning: FDA process ongoing with clarity expected in Q4, 2021
Submitted data from the histomorphometry study for inclusion in the abaloparatide label
Elacestrant:

EMERALD phase 3 trial with our partner, Menarini Group, remains on track for 2H, 2021 topline readout
RAD011:

Type C meeting with the FDA in June, 2021 for PWS phase 3 protocol review
RAD011 previous data to be presented at the PWSA/USA conference June 23-25, 2021
Additional orphan indications being assessed with 2H, 2021 timetable to finalize plan(s)
Hired Head of Science and Technology for CBD, cannabinoid derivatives, formulations and delivery
First Quarter 2021 Financial Results

Three Months Ended March 31, 2021

Net Loss
For the three months ended March 31, 2021, Radius reported a net loss of $15.7 million, or $0.34 per share, compared to a net loss of $37.7 million, or $0.81 per share, for the three months ended March 31, 2020.

For the three months ended March 31, 2021, non-GAAP adjusted net loss, was $8.6 million, or $0.18 per share, compared to non-GAAP adjusted net loss of $27.4 million, or $0.59 per share, for the three months ended March 31, 2020.

Revenue
For the three months ended March 31, 2021, TYMLOS net product revenues were $45.3 million compared to approximately $47.9 million for the three months ended March 31, 2020.

For the three months ended March 31, 2021, license revenue was $11.0 million. No license revenue was recognized for the three months ended March 31, 2020.

Costs and Expenses
For the three months ended March 31, 2021, research and development expense was $31.4 million compared to $39.0 million for the three months ended March 31, 2020, a decrease of $7.6 million, or 19%. This decrease was primarily driven by a decrease of $3.3 million in abaloparatide-TD program cost, a $4.8 million decrease in compensation expense, which is comprised of a $1.1 million decrease in compensation expense and $3.7 million of billed reimbursable expenses, and a $7.7 million decrease in elacestrant program costs, which is comprised of a $2.9 million increase in gross program expenses offset by $10.6 million of billed reimbursable expenses. These decreases were partially offset by a $5.3 million increase in abaloparatide-SC program costs and a $2.9 million increase in professional fees and other expenses.

For the three months ended March 31, 2021, selling, general and administrative expenses were $34.1 million compared to $36.4 million for the three months ended March 31, 2020, a decrease of $2.3 million, or 6%. This decrease was primarily the result of a $0.4 million decrease in travel and entertainment expenses, a $3.6 million decrease in compensation cost, and a $0.4 million decrease in other operating costs. These decreases were partially offset by a $1.9 million increase in professional support costs, and a $0.2 million increase in occupancy and depreciation costs

On May 7, 2021 Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported that David Meline, Chief Financial Officer, and Lavina Talukdar, Senior Vice President & Head of Investor Relations, will participate in a fireside chat at the Bank of America 2021 Healthcare Conference on May 13th, 2021 at 11:00 a.m. ET (Press release, Moderna Therapeutics, MAY 7, 2021, View Source [SID1234579485]).

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A live webcast will be available under "Events and Presentations" in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna’s website for 30 days following the presentation.

On May 7, 2021 photonamic GmbH & Co. KG (Head office: Pinneberg, Germany; CEO: Ulrich Kosciessa, Ph.D.) ("photonamic"), a subsidiary of SBI Holdings, Inc. (Head office: Minato-ku, Tokyo; Representative Director, President and CEO: Yoshitaka Kitao) the leader in the pharmaceutical development, translation and global commercialization of 5-aminolevulinic acid ("5-ALA") (*) reported that its Canadian subsidiary SBI ALApharma Canada Inc. (Head office: Toronto, Canada; CEO & CTO, Dr. Ralph DaCosta) ("SBI Canada") has enrolled the first patient in its Pivotal Phase 3 randomized controlled trial (RCT) evaluating the safety and efficacy of PD G 506 A (5-ALA HCl) in margin assessment during breast conserving surgery (ClinicalTrials.gov Identifier: NCT04815083) (Press release, photonamic, MAY 7, 2021, View Source;co-kg-germany-enrolls-first-patient-in-pivotal-phase-3-clinical-trial-of-pd-g-506-a-5-ala-hcl-and-eagle-fluorescence-imaging-system-for-breast-conserving-surgery-301286333.html [SID1234579501]). This important milestone occurs on the heal of the company’s FDA IND clearance for the RCT on April 23, 2021. The multicenter trial involves 20 clinical centers in the United States and Canada and will use SBI Canada’s proprietary intraoperative handheld Eagle Fluorescence Imaging SystemTM to visualize PD G 506 A-induced protoporphyrin IX (PpIX) fluorescence.

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SBI Canada was established in 2019 as part of photonamic’s strategic acquisition of the oncology business from MolecuLight Inc. (Toronto, Canada). Data from an earlier Phase 2 clinical study at Princess Margaret Cancer Center demonstrated that PD G 506 A-induced PpIX fluorescence (known to be selective for cancerous tissues) can be visualized in surgical specimens and within the surgical cavity in real-time using the compact fully handheld camera of the Eagle Fluorescence Imaging SystemTM.

"We are pleased having accomplished this milestone in our development for breast cancer surgery program" explains Ulrich Kosciessa, photonamic GmbH & Co. KG’s CEO. "It is an important step on our pathway to utilize the capabilities of 5-ALA as a precursor of PpIX and its tumor selectivity together with innovative technologies to help improve the lives of cancer patients around the world. With our proprietary handheld Eagle imaging device technology of our subsidiary SBI Canada, surgeons will now be able to investigate the surgical cavity following conventional lumpectomy allowing them to identify residual disease as part of this Phase 3 trial in breast cancer surgery". "This will allow us to further develop our technology to one day benefit breast cancer patients in a manner similar to our current 5-ALA based product currently FDA approved for neurosurgery. This product similarly helps neurosurgeons around the world to perform fluorescence-guided glioblastoma surgery."

"We are delighted at achieving both FDA IND clearance and the first patient enrolled in our Pivotal Phase 3 trial within days of each other", says Dr. Ralph DaCosta, SBI Canada’s CEO & CTO. "These achievements are important markers of progress in our on-going program to investigate 5-ALA and our novel Eagle imaging technology to improve intraoperative margin assessment and fluorescence-guided surgery. Our initial focus is on breast cancer surgery, but this work lays the foundation for other cancers where real-time visualization of carcinoma during surgery is a clinical priority". "Despite the on-going COVID pandemic, our outstanding SBI Canada team, together with the support from the SBI group of companies have managed to bring us to this critical stage in clinical translation in breast cancer surgery", says DaCosta.

(*) 5-aminolevulinic acid ("5-ALA") is an endogenous amino acid derivative produced in mitochondria. Apart from its natural role as an important natural substance metabolized to heme and cytochromes serving the energy production in the mitochondrial membranes, 5-ALA is known to metabolize into the (pink/red) fluorescent compound protoporphyrin IX (PpIX) in cancer cells. This fluorescence can be detected with the appropriate instrumentation. In addition, PpIX, is a well-known photosensitizer used in photodynamic therapy of cancers.