On March 17, 2022 Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, reported financial results for the fourth quarter and year ended December 31, 2021 (Press release, Aduro Biotech, MAR 17, 2022, View Source [SID1234610242]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2021 was a very productive year for Chinook, as we initiated the phase 3 ALIGN and phase 2 AFFINITY trials for atrasentan, presented compelling phase 1/2 data in patients with IgA nephropathy for BION-1301, successfully completed IND-enabling studies for CHK-336, continued to advance multiple programs within our research pipeline and executed notable strategic partnerships including our Evotec research collaboration, formation of Sairopa B.V. for the development of non-renal assets and establishment of the SanReno Therapeutics joint venture in China," said Eric Dobmeier, president and chief executive officer of Chinook Therapeutics. "With the recent milestones we have achieved and our strong financial position, Chinook is well-positioned to continue building the leading company addressing unmet medical needs in kidney disease. During 2022, we look forward to presenting additional data from both our atrasentan and BION-1301 programs, initiating our phase 1 trial of CHK-336 and continuing to advance our preclinical pipeline for rare, severe chronic kidney diseases."

2021 and Recent Accomplishments

Atrasentan
Atrasentan is a potent and selective endothelin A (ETA) receptor antagonist that has the potential to provide benefit in multiple chronic kidney diseases by reducing proteinuria and having direct anti-inflammatory and anti-fibrotic effects to preserve kidney function. The phase 3 ALIGN trial of atrasentan is currently enrolling patients with IgA nephropathy (IgAN), and the phase 2 AFFINITY basket trial of atrasentan is currently enrolling patients with proteinuric glomerular diseases.

Enrollment of the phase 3 ALIGN trial of atrasentan continues to advance with the activation of new trial sites and expansion into additional countries. Chinook expects to report topline data from the six-month interim proteinuria endpoint analysis in 2023 to support an application for accelerated approval under Subpart H in the United States.

Chinook has completed enrollment of the IgAN patient cohort of the phase 2 AFFINITY trial, and continues to enroll the other three cohorts, including patients with focal segmental glomerulosclerosis (FSGS), Alport syndrome and diabetic kidney disease in combination with SGLT2 inhibitors. Chinook plans to present data from the IgAN patient cohort of this study in an oral presentation at the ERA Congress in May 2022, with data from one or more additional cohorts expected in the second half of 2022.

Several abstracts on atrasentan were delivered as poster presentations at nephrology conferences throughout 2021, including:

Data demonstrating endothelin pathway activation in the kidneys of patients with IgAN has a strong association with clinical progression. Atrasentan was also shown to inhibit endothelin-1 mediated transcriptional networks, including cell proliferation, inflammation and fibrosis in human mesangial cells. This translational research was conducted in collaboration with the laboratory of Matthias Kretzler, M.D., Professor of Nephrology and Professor of Computational Medicine & Bioinformatics at University of Michigan Medical School, and supports the therapeutic potential of ETA receptor blockade with atrasentan in patients with IgAN at high risk of progression. (ASN Kidney Week 2021)

Analysis of three separate single-dose, randomized phase 1 studies of atrasentan demonstrating consistent and predictable safety, tolerability and pharmacokinetic profiles in healthy Chinese, Japanese and North American adults of non-Asian descent. The consistent profile of atrasentan across these ethnicities and geographic regions, supports the inclusion of patients with IgAN in Asia, where there is an increased prevalence and potentially accelerated disease progression, in the ongoing global phase 3 ALIGN study. (ASN Kidney Week 2021)

Data demonstrating atrasentan’s effect to rapidly reduce albuminuria and downregulate intra-renal transcriptional proliferative, inflammatory and fibrotic signaling in the gddY mouse IgAN model, supporting the therapeutic potential of atrasentan in patients with IgAN to reduce proteinuria and kidney inflammation and fibrosis, key drivers of IgAN progression. (ISN WCN 2021)

Data demonstrating atrasentan’s effect to attenuate human renal mesangial cell activation induced by endothelin-1 or IgAN patient immune-derived immune complexes in a translational model system, supporting the therapeutic potential of atrasentan in patients with IgAN, not only via its well characterized effect of reducing proteinuria, but also by potentially reducing mesangial cell activation, a hallmark of IgAN. (ISN WCN 2021)
Atrasentan was granted orphan drug designation for the treatment of primary IgAN by the European Commission.
BION-1301
BION-1301 is a novel anti-APRIL monoclonal antibody currently in phase 1/2 development for patients with IgAN. BION-1301’s potentially disease-modifying approach to treating IgAN by reducing circulating levels of galactose-deficient IgA1 (Gd-IgA1) has been demonstrated preclinically as well as clinically in both healthy volunteers and patients with IgAN.

Chinook presented data from the BION-1301 phase 1 intravenous (IV) to subcutaneous (SC) bioavailability study in healthy volunteers at the ISN World Congress of Nephrology 2021, demonstrating the ability to transition to SC administration of BION-1301 in the ongoing phase 1/2 study of BION-1301.

Chinook completed enrollment of Cohort 1 of Part 3 of the ongoing phase 1/2 study of BION-1301 and presented additional patient data and follow-up from this cohort at ASN Kidney Week 2021, indicating BION-1301 was well-tolerated and caused durable reductions in Gd-IgA1, IgA, IgM, and to a lesser extent, IgG levels in patients with IgAN. BION-1301 demonstrated a greater than 50% geometric mean reduction in 24-hour urine protein creatinine ratio (UPCR) after three (n=6) to six (n=4) months of treatment, with further reductions in two patients through one year of treatment. After at least 24 weeks of treatment, patients in Cohort 1 are transitioning from IV dosing at 450 mg every two weeks to SC dosing at 600 mg every two weeks.

Enrollment of Cohort 2 of Part 3 of the ongoing phase 1/2 study of BION-1301 is ongoing. Patients in Cohort 2 receive a SC dose of 600 mg of BION-1301 every two weeks.

Chinook plans to present additional data from Cohort 1 of Part 3 in a mini-oral presentation at the ERA Congress in May 2022, with data from Cohort 2 of Part 3 expected in the second half of 2022.
CHK-336
CHK-336 is an oral small molecule lactate dehydrogenase A (LDHA) inhibitor with liver-targeted tissue distribution that Chinook is developing for the treatment of patients with primary hyperoxaluria (PH), secondary hyperoxaluria due to increased endogenous oxalate production and idiopathic stone formation.

Chinook has completed IND-enabling studies, submitted an IND and is advancing CHK-336 towards planned initiation of a phase 1 clinical trial in healthy volunteers in the first half of 2022.

CHK-336 has received rare pediatric disease designation from the U.S. Food and Drug Administration (FDA) for PH.
Precision Medicine Research & Discovery
Chinook is focused on the discovery and development of novel precision medicines for rare, severe chronic kidney diseases (CKDs) with defined genetic or molecular drivers of disease initiation and progression, and efficient development paths.

Chinook has multiple preclinical programs across the discovery, target validation, lead identification and lead optimization stages to generate future clinical pipeline candidates.

Chinook is leveraging its ongoing strategic collaboration with Evotec to identify and validate novel targets and enable patient stratification strategies through access to the NURTuRE CKD Patient Biobank, which provides comprehensive PANOMICS characterization of thousands of CKD patients with prospective clinical follow-up and retained bio-samples of urine and blood for exploratory biomarker analysis.
Corporate

In April 2021, Chinook entered into an agreement for Sairopa B.V. to acquire certain of Chinook’s non-renal assets in exchange for a 44 percent preferred equity position in Sairopa. Any future proceeds resulting from this transaction will be shared equally between Chinook and the CVR holders until October 4, 2030, after which 100 percent of the value will accrue to Chinook.

In November 2021, Chinook closed a $183.5M public offering, which included the exercise in full of the underwriters’ option to purchase additional shares of common stock.

Also in November 2021, Chinook formed SanReno Therapeutics, a 50/50 joint venture with an investor syndicate led by Frazier Healthcare Partners and Pivotal bioVenture Partners China, to develop, manufacture and commercialize kidney disease therapies in mainland China, Hong Kong, Macau, Taiwan and Singapore.
Fourth Quarter and Full Year 2021 Financial Results

Cash Position – Cash, cash equivalents and marketable securities totaled $355.1 million at December 31, 2021, compared to $250.4 million at December 31, 2020. The increase is primarily due to net proceeds from our public offering in November 2021 and at-the-market (ATM) sales of common stock under our existing ATM facility in the second quarter of 2021, partially offset by cash used in operations.

Revenue – Total revenue increased by $50.4 million and $50.8 million for the quarter and year ended December 31, 2021, respectively, compared to the same periods in 2020. The increase was primarily due to non-cash revenue of $41.2 million recognized under Chinook’s license agreement with SanReno and from a development milestone of $10.0 million recognized under the Exclusive Patent and Know-How License and Research Collaboration Agreement with Merck for MK-5890, an anti-CD27 agonist.

Expenses –
Research and development expenses for the quarter and year ended December 31, 2021 were $24.9 million and $97.0 million, respectively, compared to $21.8 million and $36.1 million, respectively, for the same periods in 2020. The increase was primarily due to external clinical and manufacturing expenses related to the atrasentan and BION-1301 clinical programs; higher employee-related costs from increased staff to build out our clinical and development capabilities; and an increase in facilities and other costs. Research and development expenses for the year ended December 31, 2021 also included an upfront fee under a collaboration agreement with Evotec.
General and administrative expenses for the quarter and year ended December 31, 2021 were $7.7 million and $31.9 million, respectively, compared to $11.0 million and $19.1 million, respectively, for the same periods in 2020. The decrease in the quarter ended December 31, 2021 compared to same period in 2020 was primarily due to higher costs related to the merger with Aduro in 2020. The increase in the year ended December 31, 2021 compared to the prior year was primarily due to higher employee-related costs from increased staff to build out our public-company infrastructure and an increase in facilities and other costs.
Expenses due to the change in fair value of contingent consideration and contingent value rights liabilities for the quarter and year ended December 31, 2021 were $5.8 million and $27.3 million, respectively, compared to $1.5 million for the same periods in 2020. These non-cash expenses are due to the quarterly revaluation of liabilities related to the Sairopa transaction and under the Merck collaboration. During the quarter ended December 31, 2021, we were notified of the achievement of a development milestone under the agreement with Merck, which resulted in an increase to the fair value of the CVR liability.
Other –
The sale of non-renal assets to Sairopa in the second quarter of 2021 resulted in a $7.2 million gain for the year ended December 31, 2021.

The development milestone received under the Merck collaboration, net of permitted deductions, will be paid to CVR holders in the second quarter of 2022.
Net Loss – Net income for the fourth quarter of 2021 was $7.5 million, or $0.15 per basic share, compared to a net loss of $49.9 million, or $1.24 per share for the same period in 2020. Net loss for the year ended December 31, 2021 was $102.9 million, or $2.26 per share, compared to a net loss of $81.6 million, or $6.20 per share for the same period in 2020.

On March 17, 2022 Aadi Bioscience, Inc. ("Aadi") (Nasdaq: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for genetically-defined
cancers with alterations in mTOR pathway genes, reported financial results for the fourth quarter and full year
ended December 31, 2021 and provided a business update (Press release, Aadi Bioscience, MAR 17, 2022, View Source [SID1234610241]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are well-positioned in 2022 with a strong team, a solid balance sheet, and a highly promising recently approved
drug," stated Neil Desai, Ph.D., Founder, President and Chief Executive Officer of Aadi. "With our recent launch of
FYARRO and a new tumor-agnostic registrational trial for nab-sirolimus underway, Aadi is on track with our
previously outlined goals and our vision of offering a new cancer treatment to underserved patient populations."

FYARRO: Recent Highlights

In February 2022, Aadi announced the launch and commercial availability of FYARRO (sirolimus protein-bound particles
for injectable suspension) (albumin-bound) for intravenous use for the treatment of adult patients with locally
advanced unresectable or metastatic malignant PEComa.
FYARRO (also known as nab-sirolimus) was added to the National Comprehensive Cancer Network
Clinical Practice Guidelines in Oncology (NCCN Guidelines) as the only preferred treatment regimen
for malignant PEComa.
A seasoned commercial team has been hired to call on key centers of excellence that target the majority of the
malignant PEComa U.S. patient population, and a distribution network has been established to support the launch
of FYARRO. Payer coverage is tracking positively, and product orders have already been received and sent to
patients in need.
Aadi opened enrollment for its Phase 2 tumor-agnostic registrational trial, PRECISION 1, to evaluate
nab-sirolimus in adult and adolescent patients 12 years and older with solid tumors harboring pathogenic
inactivating alterations in TSC1 or TSC2 genes in February 2022. The trial consists of two separate arms for TSC1 or
TSC2 alterations. Initial clinical data from PRECISION 1 are expected in the first half of 2023.
2021 Corporate Development and Operational Highlights

FYARRO Approval
On November 22, 2021, Aadi received U.S. Food and Drug Administration (FDA) approval of its first proprietary
product. FYARRO is the first and only FDA-approved treatment for advanced malignant PEComa in adults and was
approved in less than four months after the NDA acceptance, and priority review designation was announced on July
26, 2021.
Merger Completion and Public Listing on Nasdaq

On August 26, 2021, Aadi completed its merger with Aerpio Pharmaceuticals, Inc. ("Aerpio"), a publicly traded
biotechnology company (previously traded on the Nasdaq Global Select Market under "ARPO"), and the combined company
began trading on the Nasdaq Capital Market as "AADI" post-merger. As part of the merger, each share of private Aadi
common stock was converted into the right to receive 0.3172 shares of Aerpio common stock following a 15:1 reverse
split of Aerpio’s common stock.
Concurrent to the closing of the merger, the combined company closed the previously announced $155 million private
investment in a public equity (PIPE) financing of its common stock.
Board and Leadership: Key Appointments

Aadi’s board and leadership team were strengthened with the following appointments in 2021:
Emma Reeve was appointed to Aadi’s Board of Directors and as chair of the Audit Committee. Ms. Reeve brings
over 25 years of value creation in pharmaceutical, medical device and bio-pharma service companies and a
successful track record of transitioning companies from private to public.
Brendan Delaney was appointed to the role of Chief Operating Officer. Mr. Delaney has had an established
career in oncology-focused commercial leadership roles, launching multiple groundbreaking new products and
building effective and cohesive commercial teams. As Chief Commercial Officer at Immunomedics, Inc., Brendan led
the launch of TRODELVY, the first TROP-2 directed antibody-drug conjugate for the treatment of
triple-negative breast cancer. Immunomedics was acquired by Gilead Sciences, Inc. for $21 billion.
Scott M. Giacobello, CPA, was appointed to the role of Chief Financial Officer and Treasurer. Most recently,
Mr. Giacobello was the Chief Financial Officer of GW Pharmaceuticals plc until its $7.2 billion acquisition by
Jazz Pharmaceuticals.
Loretta M. Itri, M.D., FACP was appointed to the role of Chief Medical Officer. Dr. Itri’s
extensive career spans clinical and regulatory global-leadership roles at both major pharmaceutical and
biopharmaceutical companies, Dr. Itri has overseen the development and regulatory approval of multiple
therapeutic compounds. Most recently, Dr. Itri was Chief Medical Officer at Immunomedics, Inc, where she oversaw
the development program and approval of TRODELVY.
2021 Fourth Quarter and Full Year Financial Highlights

As of December 31, 2021, cash and cash equivalents totaled $149.0 million, compared to $4.5 million as of December 31,
2020. Based on our current plans, we expect cash and cash equivalents to fund operations into 2024.

For the year ended December 31, 2021, we recognized $1.0 million of license revenue related to a milestone payment
pursuant to our license agreement with EOC Pharma. This compares to the $14.0 million received during the year ended
December 31, 2020, related to the non-refundable upfront payment for the rights and license granted to EOC Pharma
under the license agreement for the further development and commercialization of FYARRO in the People’s Republic of
China, Hong Kong Special Administration Region, Macao Special Administrative Region and Taiwan.

Operating expenses for the fourth quarter were $16.9 million compared to $5.7 million in the prior year quarter. For
the year ended December 31, 2021, operating expenses totaled $112.3 million, an increase of $95.2 million compared to
$17.1 million for the same period in 2020. The increase in operating expenses for the full year ended December 31,
2021 is due primarily to a non-cash impairment charge related to an acquired contract intangible asset of $74.2
million incurred in conjunction with the merger which was previously reported in the third quarter, and increases in
research and development and general and administrative expenses.

Research and development expenses for the fourth quarter were $7.2 million compared to $5.3 million in the prior year
quarter. For the year ended December 31, 2021, research and development expenses increased approximately $4.7 million,
to $19.7 million compared to $15.0 million for the same period in 2020. This increase was primarily the result of
increased expenses associated with our clinical and commercial drug manufacturing compared to the same periods in
2020.

General and administrative expenses for the fourth quarter were $9.7 million, a $9.3 million increase over the prior
year quarter. For the year ended December 31, 2021, general and administrative expenses increased by approximately
$16.4 million, to $18.5 million from $2.1 million for the same period in 2020. This increase was primarily the result
of increased personnel expenses related to the buildout of our commercial operations and infrastructure, as well as
increased marketing expenses to prepare for the commercial launch of FYARRO in 2022. We also incurred approximately
$2.0 million of compensation expense related to former Aerpio executives as a result of the merger.

Net loss attributable to common stockholders for the fourth quarter was $16.0 million compared to net income
attributable to common stockholders of $7.8 million in the prior year quarter. Net loss attributable to common
stockholders for the year ended December 31, 2021 was $110.7 million compared with $4.5 million in the prior year,
primarily driven by the non-cash impairment charge of $74.2 million previously reported in the third quarter, and an
increase in drug manufacturing and marketing expenses to prepare for the commercial launch in 2022 which were
discussed above.

About the National Comprehensive Cancer Network (NCCN)

The NCCN is a not-for-profit alliance of 27 leading U.S. cancer centers devoted to patient care, research and
education, is dedicated to improving the quality, effectiveness and efficiency of cancer care. The intent of the NCCN
Guidelines is to assist in the decision-making process of individuals involved in cancer care – including physicians,
nurses, pharmacists, payers, patients and their families – with the ultimate goal of improving patient care and
outcomes. For more information about the National Comprehensive Cancer Network go to: View Source

About Malignant PEComa

Advanced malignant PEComa, defined by the World Health Organization as ‘mesenchymal tumors composed of distinctive
cells that show a focal association with blood-vessel walls and usually express both melanocytic and smooth muscle
markers,’ are a rare subset of soft-tissue sarcomas, with an undefined cell of origin. While there is no formal
epidemiology for malignant PEComa, it is estimated that there are about 100-300 new patients per year in the United
States. Malignant PEComas may arise in almost any body site (typically the uterus, retroperitoneum, lung, kidney,
liver, genitourinary, and gastrointestinal tract with a female predominance) and can have an aggressive clinical
course including distant metastases and ultimately death. The estimated prognosis based on retrospective reports is
12-16 months. Cytotoxic chemotherapies typically used for sarcoma show minimal benefit. Malignant PEComas have been
shown to frequently harbor mutations in the TSC1 and/or TSC2 genes that result in the activation of mTOR
pathway making it a rational therapeutic target for this disease.

About the PRECISION 1 Trial

The PRECISION 1 Trial is a multi-center, open-label, tumor-agnostic pivotal study, of nab-sirolimus designed as a
basket trial that will evaluate approximately 120 adult and adolescent patients with solid tumors harboring pathogenic
inactivating alterations in TSC1 or TSC2 genes. The trial will have two independent arms of 60 patients
each to separately evaluate patients with either TSC1 or TSC2 inactivating alterations. Aadi has
received Fast Track designation to evaluate nab-sirolimus in this indication from the FDA. The trial opened for
enrollment in February 2022.

About FYARRO

FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or
metastatic malignant perivascular epithelioid cell tumor (PEComa).

Important Safety Information

Contraindication

FYARRO is contraindicated in patients with a history of severe hypersensitivity to sirolimus, other rapamycin
derivatives, or albumin.

Warnings and Precautions

Stomatitis

Stomatitis, including mouth ulcers and oral mucositis, occurred in 79% of patients treated with FYARRO, including 18%
Grade 3. Stomatitis was most often first reported within 8 weeks of treatment. Based on the severity of the adverse
reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Myelosuppression

FYARRO can cause myelosuppression including anemia, thrombocytopenia and neutropenia. Anemia occurred in 68% of
patients; 6% were Grade 3. Thrombocytopenia and neutropenia occurred in 35% of patients each. Obtain blood counts at
baseline and every 2 months for the first year of treatment and every 3 months thereafter, or more frequently if
clinically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently
discontinue FYARRO.

Infections

FYARRO can cause infections. Infections such as urinary tract infections (UTI), upper respiratory tract infections and
sinusitis occurred in 59% of patients. Grade 3 infections occurred in 12% of patients, including a single case each of
a UTI, pneumonia, skin, and abdominal infections. Monitor patients for infections, including opportunistic infections.
Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hypokalemia

FYARRO can cause hypokalemia. Hypokalemia occurred in 44% of patients including 12% Grade 3 events. Monitor potassium
levels prior to starting FYARRO and implement potassium supplementation as medically indicated. Based on the severity
of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hyperglycemia

FYARRO can cause hyperglycemia. Hyperglycemia occurred in 12% of patients treated with FYARRO, all of which were Grade
3 events. Monitor fasting serum glucose prior to starting FYARRO. During treatment, monitor serum glucose every 3
months in non-diabetic patients, or as clinically indicated. Monitor serum glucose more frequently in diabetic
patients. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue
FYARRO.

Interstitial Lung Disease / Non-Infectious Pneumonitis

FYARRO can cause interstitial lung disease (ILD) / non-infectious pneumonitis. ILD / non-infectious pneumonitis
occurred in 18% of patients treated with FYARRO, of which all were Grades 1 and 2. Based on the severity of the
adverse reaction, withhold, reduce the dose, or permanently discontinue FYARRO.

Hemorrhage

FYARRO can cause serious and sometimes fatal hemorrhage. Hemorrhage occurred in 24% of patients treated with FYARRO,
including Grade 3 and Grade 5 events in 2.9% of patients each. Monitor patients for signs and symptoms of hemorrhage.
Based on the severity of adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hypersensitivity Reactions

FYARRO can cause hypersensitivity reactions. Hypersensitivity reactions, including anaphylaxis, angioedema,
exfoliative dermatitis, and hypersensitivity vasculitis have been observed with administration of the oral formulation
of sirolimus. Hypersensitivity reactions including anaphylaxis have been observed with human albumin administration.
Monitor patients closely for signs and symptoms of infusion reactions during and following each FYARRO infusion in a
setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients for at least 2
hours after the first infusion and as clinically needed for each subsequent infusion. Reduce the rate, interrupt
infusion, or permanently discontinue FYARRO based on severity and institute appropriate medical management as needed.

Embryo-Fetal Toxicity

Based on animal studies and the mechanism of action, FYARRO can cause fetal harm when administered to a pregnant
woman. In animal studies, mTOR inhibitors caused embryo-fetal toxicity when administered during the period of
organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting
dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to avoid
becoming pregnant and to use effective contraception while using FYARRO and for 12 weeks after the last dose.

Male Infertility

Azoospermia or oligospermia may be observed in patients treated with FYARRO. FYARRO is an anti-proliferative drug and
affects rapidly dividing cells such as germ cells.

Immunizations and Risks Associated with Live Vaccines

No studies in conjunction with immunization have been conducted with FYARRO. Immunization during FYARRO treatment may
be ineffective. Update immunizations according to immunization guidelines prior to initiating FYARRO, if possible.
Immunization with live vaccines is not recommended during treatment and avoid close contact with those who have
received live vaccines while on FYARRO. The interval between live vaccinations and initiation of FYARRO should be in
accordance with current vaccination guidelines for patients on immunosuppressive therapies.

Risk of Transmission of Infectious Agents with Human Albumin

FYARRO contains human albumin, a derivative of human blood. Human albumin carries only a remote risk of transmission
of viral diseases because of effective donor screening and product manufacturing processes. A theoretical risk for
transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral
diseases or CJD have ever been associated with albumin.

Adverse Reactions

Adverse Reactions in PEComa

The most common adverse reactions (≥30%) were stomatitis in 27 (79%) patients; fatigue and rash in 23 (68%) patients
each; infection in 20 (59%) patients; nausea and edema in 17 (50%) patients each; diarrhea, musculoskeletal pain and
decreased weight in 16 (47%) patients each; decreased appetite in 15 (44%) patients; cough in 12 (35%) patients; and
vomiting and dysgeusia in 11 (32%) patients each.

Laboratory Abnormalities in PEComa

The most common Grade 3 to 4 laboratory abnormalities (≥6%) were decreased lymphocytes in 7 (21%) patients; increased
glucose and decreased potassium in 4 (12%) patients each; decreased phosphate in 3 (9%) patients; and decreased
hemoglobin and increased lipase in 2 (6%) patients each.

Dosage interruptions

Dose interruptions of FYARRO due to an adverse reaction occurred in 22 (65%) patients. Adverse reactions which
required dosage interruption in >5% of patients included stomatitis in 6 (18%) patients, pneumonitis in 5 (15%)
patients, anemia in 3 (9%) patients, and dehydration, dermatitis acneiform, and thrombocytopenia in 2 (6%) patients
each.

Dose reduction

Dose reductions of FYARRO due to an adverse reaction occurred in 12 (35%) patients. Adverse reactions which required
dose reductions in > 5% of patients included stomatitis and pneumonitis in 3 (9%) patients each.

Drug Interactions

Reduce the dosage of FYARRO to 56 mg/m2 when used concomitantly with a moderate or weak cytochrome P-450
3A4 (CYP3A4) inhibitor. Avoid concomitant use with drugs that are strong CYP3A4 and/or P-glycoprotein (P-gp)
inhibitors and inducers and with grapefruit and grapefruit juice.

Use in Specific Populations

Pregnancy

Based on the mechanism of action and findings in animals, FYARRO can cause fetal harm when administered to a pregnant
woman. Advise females of the potential risk to a fetus and to avoid becoming pregnant while receiving FYARRO.

Lactation

Sirolimus is present in the milk of lactating rats. There is potential for serious adverse effects from sirolimus in
breastfed infants based on mechanism of action. Because of the potential for serious adverse reactions in breastfed
infants from FYARRO, advise women not to breastfeed during treatment with FYARRO and for 2 weeks after the last dose.

Females and Males of Reproductive Potential

FYARRO can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of
reproductive potential prior to starting treatment with FYARRO. Advise females of reproductive potential to use
effective contraception and avoid becoming pregnant during treatment with and for at least twelve weeks after the last
dose of FYARRO. Advise males with female partners of reproductive potential to use effective contraception and avoid
fathering a child during treatment with FYARRO and for at least twelve weeks after the last dose of FYARRO. Although
there are no data on the impact of FYARRO on fertility, based on available clinical findings with oral formulation of
sirolimus and findings in animals, male and female fertility may be compromised by the treatment with FYARRO.

Pediatric

The safety and effectiveness of FYARRO in pediatric patients have not been established.

Geriatric Use

Of the 34 patients treated with FYARRO, 44% were 65 years of age and older, and 6% were 75 years of age and older.
Clinical studies of FYARRO did not include sufficient numbers of patients aged 65 and over to determine whether they
respond differently from younger patients.

Hepatic Impairment

FYARRO is not recommended for use in patients with severe hepatic impairment. Reduce FYARRO dosage in patients with
mild or moderate hepatic impairment.

On March 17, 2022 Race Oncology Ltd (ASX:RAC) reported that it has received interim results from an extramedullary acute myeloid leukaemia (AML) preclinical program that suggest that its asset, Zantrene, in combination with decitabine, can kill AML tumours in a mouse model of extramedullary AML (Press release, Race Oncology, MAR 17, 2022, View Source [SID1234610228]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The research, led by eminent cancer researcher Associate Professor Nikki Verrills of The University of Newcastle and Hunter Medical Research Institute, found that low dose Zantrene in combination with decitabine can kill AML tumours in a mouse model.

Difficult-to-treat disease
Extramedullary AML occurs when the leukaemia spreads from the bone marrow and forms solid tumours in tissues such as the skin, breast, kidney, brain or other organs. A 2020 prospective positron imaging trial identified that up to 22% of AML patients have the extramedullary form.

Patients with extramedullary AML have no clinically approved treatments and only limited experimental treatment options. Many clinical trials exclude patients with this difficult-to-treat form of AML.

Combination of Zantrene and decitabine
In a 2020 Phase 2 clinical trial conducted at Chaim Sheba Medical Centre, Tel Aviv, in relapsed and refractory AML patients, Zantrene was observed to have clear efficacy in patients with extramedullary AML.

On the basis that Zantrene is a potent FTO inhibitor, it was hypothesised that Zantrene and decitabine would synergise to better kill AML cells.

This hypothesis was tested both in vitro in AML cell cultures and in vivo in a mouse model of extramedullary AML.

These findings build on the results of earlier AML clinical trials and reveal that:

Zantrene in combination with decitabine was found to target extramedullary tumours as well as in the bone marrow and spleen using an AML mouse model;
Zantrene alone found to kill a genetically diverse range of AML cells at low drug concentrations and slow the growth of AML tumours in mice; and
Zantrene in combination with decitabine showed significantly greater cell killing across a diverse panel of AML cell lines than either drug on its own (true synergy).
RAC chief executive officer Phillip Lynch said, "These results provide support for our well advanced extramedullary AML clinical trial and provides important guidance for the study’s design and treatment protocol."

Next steps
Race Oncology is rapidly advancing Zantrene into the clinic as a possible new treatment option for patients with extramedullary AML.

The company will conduct further mouse studies to explore optimal dosing schedules to report in the second quarter of 2022 and is pursuing publication of results in a high impact, peer-reviewed journal.

Race is now initiating clinical studies using low dose Zantrene and decitabine in combination to treat patients with extramedullary AML or MDS who cannot tolerate, or who are unwilling to tolerate, high-intensity chemotherapy.

This trial is expected to begin patient recruitment in the next quarter.

"The results from Professor Verrills’ laboratory are highly supportive of our upcoming extramedullary AML Phase 1/2 trial for Zantrene," RAC chief scientific officer Dr Daniel Tillett said.

"This work further builds on the 2020 Phase 2 trial of Prof Arnon Nagler, who identified Zantrene as showing encouraging efficacy in extramedullary AML.

"The optimised drug combination and schedule identified in this preclinical mouse study will be rapidly translated to the clinic via our extramedullary AML trial."

RAC shares have been as much as 5.8% higher this morning to A$2.75.

On March 17, 2022 Oasmia Pharmaceutical AB, an oncology-focused specialty pharmaceutical company, reported the planned upgrade of its Research and Development laboratory facility for formulations intended to treat cancers (Press release, Oasmia, MAR 17, 2022, View Source [SID1234610227]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The laboratory facilities, in Uppsala, Sweden, are being upgraded to provide greater capacity to handle these formulations which include new formulations of Cantrixil and formulations using Oasmia’s proprietary drug delivery platform.

Oasmia acquired the global development and commercialization rights for Cantrixil from Kazia Therapeutics, an Australian oncology-focused biotechnology company in March 2021. Following the publication of positive Phase I results, Oasmia is now preparing for the initiation of a Phase II trial of an intraperitoneal formulation of Cantrixil in advanced ovarian cancer. Oasmia will, among other things, be developing a preclinical intravenous formulation of Cantrixil which will be developed at the new facility in Uppsala.

Kai Wilkinson PhD., Chief Technical Officer of Oasmia, commented "With this new laboratory facility, we will be expanding our capabilities to provide novel developments and formulations. Not only will we be able to formulate new compounds for further clinical testing, but we will also be able to handle more advanced synthesis work, if required."

On March 17, 2022 Invitae (NYSE: NVTA), a leading medical genetics company, reported full access to its Personalized Cancer Monitoring (PCMTM) platform to help detect minimal or molecular residual disease (MRD) in patients with solid tumors (Press release, Invitae, MAR 17, 2022, View Source [SID1234610226]). Invitae PCM uses a novel set of personalized assays based on a patient’s tumor to detect circulating tumor DNA (ctDNA) in blood, offering the ability to perform risk stratification, response assessment to treatment and detection of cancer recurrence, based on recent studies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

"Relapse risk stratification is a clinical need for many patients undergoing treatment for solid tumors and is best served by up-to-date molecular tools to complement and improve upon the standard of care methods for recurrence detection," said Robert Nussbaum, M.D., chief medical officer, Invitae. "The PCM platform complements current monitoring methods, and has the ability to determine a cancer therapy’s effectiveness earlier than those methods for many patients, allowing clinicians the opportunity to refine treatment options."

Over the past several years, research from Invitae and the greater scientific community, including the TRACERx study led by Professor Charles Swanton at the Francis Crick Institute and University College London (UCL), and funded by Cancer Research UK, has shown that MRD monitoring can reliably identify lung cancer patients at high risk of relapse, detect post-surgical recurrence often earlier than standard imaging, assess therapy response, and potentially act as a surrogate for clinical trial endpoints. With these capabilities, MRD monitoring promises to shorten clinical trials and accelerate the development of potentially life-saving new drugs. Invitae PCM is a pan-cancer, tumor-informed liquid biopsy assay, co-developed with the TRACERx consortium, that uses a next generation sequencing (NGS) to analyze ctDNA in a patient’s plasma.

"MRD is an important biomarker in the adjuvant and surveillance period," said Professor Charles Swanton, MBPhD, FRCP, FMedSci, FRS, FAACR, at the Francis Crick Institute and UCL Cancer Institute and Chief Clinician of Cancer Research UK. "As we’ve seen in the TRACERx study, PCM provides prognostic information, can aid in cases of radiographic ambiguity, and demonstrates high clinical sensitivity and specificity."

Liquid biopsy tests have been available for therapy selection, but to identify MRD at an earlier stage than conventional methods before patients clinically relapse, the technology must be sensitive enough to detect ctDNA at very low levels. Additionally, an MRD test with high specificity is also needed to reduce the likelihood of false positive results. The PCM test utilizes advanced technologies to arrive at high levels of sensitivity and specificity, detecting tumor DNA at very low levels of concentrations in peripheral blood. Validation studies demonstrate greater than 99.9% sensitivity in detecting ctDNA at a 0.008% variant allele frequency.

"We are excited about PCM availability globally, as this is an evolving area where we have invested over the last year and we believe has the potential to give patients the information needed to understand their recurrence risk to fight and beat the disease," said Sean George, Ph.D., co-founder and CEO of Invitae.

Each assay is custom designed to detect a patient’s unique tumor signature, allowing for personalized results to guide treatment decisions. Invitae PCM requires both blood and tumor tissue samples from the patient to conduct tumor-normal whole exome sequencing (WES). Based on the results, Invitae’s proprietary algorithm selects 18-50 tumor-specific variants to include on the patient’s custom-designed ctDNA panel. This range of variants allows for a balance of highly sensitive and specific MRD detection in cancers that have lower or higher mutational burdens.

If an MRD-positive result is obtained at any point in a cancer patient’s journey, the clinician and patient can discuss the implications of the result and the most appropriate treatment or clinical trial options. "This molecular knowledge impacts cancer patients throughout their cancer journey, making this a mainstay in precision oncology," said George.

Invitae is actively expanding the research portfolio globally to continue to gather data on PCM clinical utility as well as MRD-guided studies. Invitae anticipates multiple publications this year across its PCM studies in lung, breast, head and neck, and GI tumors as well as several prospective studies kicking off in the first half of the year. These prospective studies include a pan-tumor study (MARIA) and several studies in breast and GI cancers, including ARTEMIS, a study examining Invitae’s PCM offering specifically for patients with pancreatic cancer. The study will be conducted in partnership with a high profile institution near Tokyo, the National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Sample collection will begin in Q2 2022.