Swiss Researchers ID 76 Potential Abnormal Protein Biomarkers in Parkinson’s Disease

Researchers at ETH Zurich identified 76 potential abnormal proteins in Parkinson’s disease patients that may be useful as biomarkers for the disease. Key to the findings is that the proteins are found in both healthy and Parkinson’s patients, but have abnormal structures in Parkinson’s patients.

Led by Professor Paola Picotti, the research was published in the journal Nature Structural and Molecular Biology.

The research team wrote that “Because protein structure reflects function, we tested whether global, in situ analysis of protein structural changes provides insight into PD pathophysiology and could inform a new concept of structural disease biomarkers.”

They used limited proteolysis-mass spectrometry (LiP-MS) and identified 76 structurally changed proteins in cerebrospinal fluid in people with PD compared to healthy donors. “These proteins were enriched in processes misregulated in PD, and some proteins also showed structural changes in PD brain samples,” the authors wrote.

Their next steps will be to evaluate the markers and verify them in larger groups of patients.

“But what we’ve seen so far, they’re actually a very strong indicator for the disease,” stated Natalie de Souza, senior scientist in Paola Picotti’s team and one of the study’s co-authors.

They evaluated CSF in 50 healthy donors and 50 Parkinson’s patients, which were provided by Dutch clinicians. LiP-MS can measure structural alterations in proteins and identify exactly where those changes are situated.

Future work will be on improving the LiP-MS technique to amplify the biomarker signals in hopes of using it for disease detection. They also hope to evaluate the new bioamarkers to not only detect Parkinson’s disease, but to try to differentiate it from other neurodegenerative diseases such as Alzheimer’s.

Azura’s Phase IIb for Meibomian Gland Dysfunction Trial Hits Co-Primary Endpoints

November 17, 2022

Meibomian Gland Dysfunction, or MGD, is a disease of the eyes that is caused by abnormal keratin production that causes blocked glands. This affects the amount and quality of meibum secretions in the upper and lower eyelids, causing inflammation of the surface of the eye, dry eye, pain, irritation and vision problems.

Tel Aviv, Israel and Melbourne, Australia-based Azura Ophthalmics announced positive three- months efficacy and safety data from a Phase IIb trial of AZR-MD-001 0.5% in MGD. The study hit the co-primary endpoints, improvements in Meibomian Glands Yielding Liquid Secretion (MGYLS, or the number of open glands), and Ocular Surface Disease Index (OSDI, or improved symptoms).

It also hit other clinically meaningful endpoints, such as improvements in meibum quality, improvements in tear stability, and improvements across multiple patient-reported outcome measures (SPEED and average VAS).

The drug is an ointment applied directly to the meibomian glands in the lower eyelid. The company says that the drug, which “harnesses the power of selenium sulfide” (their words), dissolves the bonds between abnormal keratin proteins, resulting in a softening of the blockage and slower keratin production.

“At Azura, we are taking a completely new approach to treating MGD which is the root cause of many downstream ocular surface conditions,” noted Marc Gleason, Azura’s CEO.

Gleeson went on to say, “These data clearly demonstrate consistency in efficacy across multiple sign and symptom endpoints. With as little as four applications of AZR-MD-001, improvement in glandular function was observed and continued to improve over three months. We are thrilled to build upon these positive results by advancing AZR-MD-001 to a pivotal Phase III clinical trial for MGD in 2023.”

According to a Coherent Market Insights report issued in 2021, the U.S. market alone was $1.976 billion in 2020 and expected to increase by a CAGR of 15.4% from 2020-2030. Other treatments on the market include TearScience’s LipiFlow and LipiScan. TearScience is a subsidiary of Johnson and Johnson Vision Care. Allergen, now AbbVie, has the Refresh Repair Lubricant Eye Drops. And OASIS Medical has Oasis Tears Omega 3 and Oasis Tears Vision.

Clinical Trial Update, July 15, 2022

And closing out the week, there were four clinical trial updates. Take a look.

Omega Therapeutics reported the FDA had cleared it for a Phase I/II trial of OTX-2002. The drug is an epigenetic controller that in preclinical studies suppressed MYC mRNA levels in the liver. It is being developed for hepatocellular carcinoma.

CANbridge Pharmaceuticals dosed the first patient in China in the Phase II EMBARK study of CAN108 (maralixibat) in biliary atresia. The trial will evaluate the drug in patients with BA after Kasai surgery. It is expected to enroll up to 20 patients in China and 72 patients globally. CANbridge and Mirum Pharmaceuticals have an exclusive license deal for the drug in Greater China. The drug (Livmarli) is an oral, once-daily, ileal bile acid transporter inhibitor. It is approved in the U.S. for cholestatic pruritus in patients with Alagille syndrome one year of age and older.

EyePoint Pharmaceuticals announced 12-monht data form the Phase I “Durasert and Vorolanib in Opthalmology” (DAVIO) trial of EYP-19001 for wet age-related macular degeneration as a potential twice-a-year treatment. The product is a sustained delivery anti-vascular endothelial growth factor (anti-VEGF) therapy. The data demonstrated continued positive safety and efficacy profile with promising curability.

Escend Pharmaceuticals received the go-ahead from the FDA to initiate a Phase I trial of ES-3000 for r/r AML. ES-3000 is an oral small molecule that ablates leukemic stem cells by reducing beta-catenin expression via a novel mechanism of action.

Clinical Trial Update, July 14, 2022

It has been a surprisingly quiet day for clinical trial news today. Here’s a look.

LG Chem enrolled the first participant in a Phase I trial of LG203003 for non-alcoholic steatohepatitis (NASH). The drug is formulated to suppress the accumulation of fat in liver cells by selectively impeding the activation of DGAT2, a triglyceride synthetase.

Xequel Bio announced positive results from a Phase Ib trial of iNexin (aCT1 ophthalmic solution) for corneal injury in patients with dry eye disease. The data showed the drug was safe and well-tolerated with early efficacy signals observed.

Regeneron Pharmaceuticals and Sanofi announced positive results from a Phase III trial of Dupixent (dupilumab) in kids ages one to 11 years with eosinophilic esophagitis (EoE). Dupixent has been approved globally for atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) or EoE in other age groups. There are no approved treatments for EoE for children under the age of 12.

HHS Reminds Pharmacies: You’re Obligated to Stock Abortion Drugs

July 13, 2022

Now that the Supreme Court tossed out Roe v. Wade with its Dobbs decision, the U.S. Department of Health and Human Services (HHS) issued guidance to the country’s retail pharmacies, reminding them of their “Obligations under Federal Civil Rights Laws to Ensure Access to Comprehensive Reproductive Health Care Services.”

Pointing to the approximately 60,000 retail pharmacies in the U.S., the guidance “covers the nondiscrimination obligations of pharmacies under federal civil rights laws.”

Under Section 1557 of the Affordable Care Act and its implementing regulations (45 C.F.R. part 92), people who receive federal financial assistance can’t be excluded as an individual from “participating in, denying them the benefits of, or otherwise subjecting them to discrimination on the basis of sex and disability, among other bases, in their health programs and activities.”

And that also means pharmacies can’t discriminate against pharmacy customers with medications, such as “making determinations regarding the suitability of a prescribed medication for a patient; or advising patients about medications and how to take them.”

The guidance notes that the U.S. has the highest maternal mortality rate among developed countries, although most are preventable. They have, however risen over the last twenty years with maternal deaths particularly high among Black women and Native American women regardless of income or education levels. The Dobbs v. Jackson Women’s Health Organization decision, the guidance says, “will exacerbate these inequities and disparities for women across the country. Further, the early loss of pregnancy (before 13 completed weeks) is extremely common, experienced by about 10% of those who know they are pregnant.”

HHS is committed to improving maternal health, including people who experienced miscarriages, and plan to enforce civil rights laws as a way to improve that public health situation. They add, “Discrimination against pregnant people on the basis of their pregnancy or related conditions is a form of sex discrimination.”

They go on to describe these related conditions: early pregnancy lost and a health care providers prescribes pretreatment with mifepristone followed by misoprostol to assist with the passing of the miscarriage; severe and chronic stomach ulcers that might require misoprostol to decrease risk of serious complicated (“if the pharmacy refuses to fill the individual’s prescription or does not stock misoprostol because of its alternate uses, it may be discriminating on the basis of disability”); a person with a bleeding disorder scheduled for a surgical abortion and the health care providers prescribes hemoglobin or hematocrit to decrease the risk of hemorrhage; a person reporting to the ER with chills, fever and vaginal bleeding diagnosed with a miscarriage complicated by a uterine infection (septic abortion) and orders an antibiotic; a person undergoing fertility treatments receiving a positive pregnancy, but has symptoms associated with an ectopic pregnancy and is then diagnosed as such and the physician orders methotrexate to halt the pregnancy; and several others.

HHS also emphasizes that it enforces the Church Amendments, which protect health care personnel from discrimination related to their employment because they refuse to perform or assist in the performance of abortion or sterilization because of their religious believes or morals.

Clinical Trial Updates, July 13, 2022

Here’s a peek at some of today’s top clinical trial announcements.

Atara Biotherapeutics announced that its Phase II EMBOLD study of ATA188 in progressive multiple sclerosis will continue with no sample size adjustment after interim analysis by the Independent Data and Safety Monitoring Committee. ATA188 is a T-cell-based off-the-shelf therapeutic that targets Epstein-Barr virus (EBV)-infected B cells and plasma cells.

Humanigen reported that the ACTIV-5/BET-B trial conducted by the NIH evaluating its lenzilumab and Gilead Sciences’remdesivir for COVID-19 did not hit statistical significance of decreased number of hospitalized patients under the age of 85 with baseline CRP who remained alive and without the need for mechanical ventilation after 29 days of treatment. Lenzilumab is a first-in-class antibody targeting granulocyte-macrophage colony-stimulating factor (GM-CSF).

Merit Medical Systems enrolled the first patient in its Canadian prospective, post-market observation study of SCOUT, a wireless, radar-guided localization system to assist breast surgeons in IDing biopsied tumors for removal during breast-conserving surgery.

Endevica Bio dosed the first patient in its Phase I trial of TCMCB07 for cachexia. TCMCB07 is a melanocortin-4 antagonist peptide. Cachexia is a life-threatening aspect of many diseases, including lack of appetite and loss of muscle disproportionate to the decrease in caloric intake. The study will enroll up to 97 healthy volunteers with data expected in the first quarter of 2023.

Bio-Thera Solutions dosed the first patients in a Phase I trial of BAT8006 for advanced solid tumors. The drug is an antibody drug conjugate that targets folic acid receptor alpha.

Pluristem Therapeutics announced topline results from its Phase III trial of allogeneic PLX-PAD cells for muscle injury after arthroplasty for hip fracture. PLX-PAD was shown to be effectively accelerate muscle strength and regeneration, but did not meet the primary endpoint, which was the Short Physical Performance Battery (SPPB) test at week 26.

SaNOtize Research & Development Corp. published data from a Phase III trial of their nitric oxide nasal spray (NONS) for adults with COVID-19. Starting treatment within three days of a positive test, viral load was decreased by about 94% within 24 hours and 99% within 48 hours in patients at higher risk of disease progression.

Clinical Trial Announcements, July 12, 2022

Here’s a look at some of today’s leading clinical trial announcements.

Verve Therapeutics dosed the first patient in a Phase Ib study of VERVE-101 for familial hypercholesterolemia. VERVE-101 is a CRISPR-based therapy designed to turn off the PCSK9 gene in the liver.

Pulmatrix dosed the first five patients in a phase I study of PUR3100 for acute migraine. PUR3100 is a novel pulmonary inhaled formulation of dihydroergotamine (DHE).

scPharmaceuticals announced positive results from the AT HOME-HF Pilot Phase II study of FUROSCIX (furosemide 80 mg/10 mL for SQ administration) for heart failure. The study enrolled 41 patients, 34 of whom received FUROSCIX and 17 received “treatment as usual.” The patients had chronic heart failure who presented to a heart failure clinic with worsening congestion and requiring augmented diuresis.

Clinilabs Drug Development Corporation initiated enrollment of a Phase I/IIa trial of CYB003 for major depressive disorder. The drug is the first novel psilocybin analog to be evaluated for this indication.

Edgewise Therapeutics initiated enrollment of the Phase II CANYON trial of EDG-5506 for people with Becker Muscular Dystrophy (BMD). EDG-5506 is an oral small molecule myosin modulator designed to protect injury-susceptible fast skeletal muscle fibers in dystrophinopathies.

Aldeyra Therapeutics announced that its clinical trial had hit both primary endpoints of Ocular Redness and Schirmer Test in its evaluation of reproxalap for dry eye disease. Reproxalap is an investigational first-in-class small molecular RASP modulator.

Dyne Therapeutics received clearance in New Zealand to initiate a Phase I/II MAD trial of DYNE-101 in patients with myotonic dystrophy type 1 (DM1). DYNE-1 consists of an antigen-binding fragment antibody (Fab) conjugated to an antisense oligonucleotide (ASO) to enable targeted muscle tissue delivery with the hopes of decreasing toxic DMPK RNA in the nuclease, releasing splicing proteins and allowing normal mRNA processing and translation of normal proteins.

Clinical Trial Update, Monday, July 11, 2022

Here’s a look at some of today’s clinical trial updates.

MacroGenics shuttered a Phase II trial of enoblituzumab in combination with retifanlimab or tebotelimab as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). There were seven reported deaths. Enoblituzumab is an anti-B7-H3 monoclonal antibody. Both retifanlimab and tebotelimab are anti-PD-1 checkpoint inhibitors.

Myrtelle reported positive efficacy data from its ongoing Phase I/II trial Phase I/II trial of its rAAV-Olig001-ASPA gene therapy in Canavan Disease. They had encouraging early efficacy data and a favorable safety profile in the first three patients treated. The trial uses the company’s rAAV vector to directly target oligodendrocytes, the affected bran cells in the disease.

Telix Pharmaceuticals dosed the final patient and completed recruitment in the Phase III ZIRCON study of its investigational kidney cancer imaging agent TLX250-CDx. The study dosed 300 patients so far. The product has received Breakthrough Designation status from the FDA.

Aquestive Therapeutics announced positive topline data from the final two arms of Part 3 of the EPIPHAST study for AQST-109 epinephrine oral film. The trial is evaluating the administration of the film under different conditions. In this case, peanut allergy.

Lipocrine reported the FDA has accepted its IND application for LPCN 2101 for epilepsy. The company plans to launch a Phase II trial of the drug in photosensitive epilepsy. The drug is an oral, endogenous neuroactive steroid, a positive allosteric modulator of GABA_A receptor.

Exelixis announced that its Phase III COSMIC-313 Trial hit the primary endpoint, demonstrating significant improvement in progression-free survival (PFS). The study is evaluating the combination of Cabometyx (cabozantinib), Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) compared to the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk renal cell carcinoma (RCC). Cabometyx is a tyrosine kinase inhibitor approved for RCC.

Biomica and a subsidiary of Evogene enrolled the first patient in its Phase I study of BMC128 with Bristol Myers Squibb’s Opdivo. BMC128 is a rationally designed microbial consortium identified and chosen via a detailed functional microbiome analysis using the company’s PRISM high-resolution microbiome analysis platform. It is made up of four unique bacterial strains that harbor specific functional capabilities with the potential to improve immunological therapeutic response.

Overland ADCT BioPharma dosed the first patient in China with Zynlonta in combination with rituximab compared to standard immunochemotherapy in the Phase III LOTIS-5 study in second-line or later, transplant ineligible patients with diffuse large B-cell lymphoma (DLBCL). Zynlonta (loncastuzimab tesirine-lpyl) is a CD19-directed antibody drug conjugate (ADC).

Genentech announced primary analysis of the Phase III HAVEN 6 study of Hemlibra (emicizumab-kxwh) in moderate or mild hemophilia A, without factor VIII inhibitors. The primary analysis included data from 72 participants who warranted prophylaxis.

Sanofi reported on the Phase III ATLAS-PPX study which demonstrated that fitusiran dosed once a month showed a 61% decrease in the annualized bleed rate (ABR) over a seven-month follow-up period versus previous therapy with either blood clotting factor replacement or bypassing agents (BPAs). Fitusiran is an RNA interference (RNAi) therapeutic that targets antithrombin. The company also presented data on the Phase III XTEND-1 study, which compared efanesoctocog alfa therapy to patients receiving previous treatment with clotting factor replacement. The trial hit the primary efficacy endpoint, with once-weekly efanesoctocog alfa prophylaxis demonstrating clinically meaningful bleed protection for severe hemophilia A patients.

Novo Nordisk also reported Phase III data at the conference this weekend. Its concizumab is an anti-tissue factor pathway inhibitor (TFPI) antibody for once-daily prophylactic treatment for all types of hemophilia. The data demonstrated an 86% decrease in treated spontaneous and traumatic bleeds when on concizumab prophylaxis, with an estimated mean ABR of 1.7 compared to 11.8 with no prophylaxis. This was the primary endpoint. The overall median ABR was zero, compared to 9.8 for no prophylaxis.

Broad View of Clinical Trials This Week

With the end of the American Society of Clinical Oncology (ASCO) annual meeting and the start of the American Headache Society (AHS) meeting, as well as other major meetings, it was an extremely busy week for clinical trial updates and news. Here’s a look.

COVID-19-Related

Merck & Company and Ridgeback Therapeutics published additional data from the Phase III MOVe-OUT trial of Lagevrio (molnupiravir) in non-hospitalized adults with mild to moderate COVID-19 at high risk for progressing to severe disease. Molnupiravir is an antiviral drug.

AstraZeneca published results from its Phase III TACKLE trial of Evusheld (tixagevimab and cilgavimab) for early outpatient treatment of mild-to-moderate COVID-19. The results demonstrated that a single 600mg dose of the antibody cocktail significantly decreased the relative risk of progressing to severe COVID-19 or death by 50% through day 29 compared to placebo.

Immunome enrolled the first patient in a Phase Ib trial of IMM-BCP-01 for treatment of COVID-19. The therapy is a three-antibody cocktail.

Moderna announced that its Omicron-containing COVID-19 booster candidate, mRNA-1273.214 demonstrated superior antibody response against Omicron in its Phase II/III study. The vaccine contains the original COVID-19 vaccine, Spikevax, as well as a vaccine targeting the Omicron variant. In the study, the 50-microgram booster dose of the bivalent vaccine hit all pre-specified endpoints. These included superior neutralizing antibody against the Omicron variant one month after dosing compared to the original Spikevax vaccine. The dose of the bivalent vaccine was generally well-tolerated, with side effects similar to what was seen with the original Spikevax shots. The company also announced it had dosed the first patients in a Phase III trial of its seasonal influenza vaccine candidate, mRNA-1010. It is expected to enroll about 6,000 adults in the Southern Hemisphere. It is designed to evaluate the safety and immunological non-inferiority of the mRNA flu shot compared to a licensed seasonal flu vaccine in adults 18 years and older.

Non-COVID-19-Related

BioNTech presented preliminary Phase I data of its BNT122 it is evaluating with Genentech in pancreatic cancer. The Phase I trial is studying the mRNA-based individualized neoantigen specific immunotherapy (iNeST) autogene cevumeran (BNT122) in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 immune checkpoint inhibitor, and chemotherapy. The patients in the study have resected pancreatic ductal adenocarcinoma (PDAC). The early data demonstrated a favorable safety profile and encouraging indications of clinical activity. BNT122 is being developed in multiple solid tumor indications.

Eli Lilly and Boehringer Ingelheim presented data at the American Diabetes Association Scientific Sessions 2022 in New Orleans suggesting their Jardiance (empagliflozin) demonstrated a decreased risk of hospitalization for heart failure by 50%. The two companies presented data from two analyses of the final U.S. data from the EMPagliflozin comparative effectiveness and SafEty (EMPRISE) real-world study. The results demonstrated Jardiance reduced the risk of hospitalization for heart failure compared to two other classes of glucose-lowering drugs in adults with type 2 diabetes. It showed relative risk decreases of 50% compared to DPP-4 inhibitors and 30% compared to GLP-1 receptor agonists.

Novartis announced Tafinlar (dabrafenib) + Mekinist (trametinib) significantly improved efficacy in patients ages 1 to 17 years old with BRAF V600 pediatric low-grade glioma (pLCC) requiring first systemic treatment compared to chemotherapy. The combination are BRAF/MEK inhibitors.

Portage Biotech presented early data from its Phase I/II trial of PORT-2 for melanoma and non-small cell lung cancer. The drug is an invariant natural killer T cell (iNKT) agonist.

Arcutis Biotherapeutics announced positive topline results from the STRATUM Phase III trial of roflumilast foam for adolescents and adults with moderate to severe seborrheic dermatitis. Roflumilast foam 0.3% is a once-daily topical foam formulation of a highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor.

Apexigen published results from the Phase II PRINCE study showcasing distinct biosignatures in metastatic pancreatic cancer patients treated with sotigalimab and/or nivolumab in combination with chemotherapy. Sotigalimab is an agonistic CD40 antibody. Nivolumab is Bristol Myers Squibb’s PD-1 inhibitor, Opdivo.

Arbutus Biopharma and Vaccitech dosed the first patient in a Phase IIa trial of AB-729 with VTP-300 and standard-of-care nucleotides reverse transcriptase inhibitor therapy for virologically-suppressed chronic HBV infection (cHBV). AB-729 is Arbutus’ RNAi candidate. VTP300 is Vaccitech’s T-cell stimulating immunotherapeutic.

Enterome announced proof-of-concept immune response data and first clinical data from its Phase I/II trial of EO2401 in combination with BMS’s Opdivo in non-resectable adrenocortical carcinomas (ACC), treated with at least one line, but not more than two previous lines of systemic therapy, or without prior systemic therapy for advanced/metastatic disease. EO2401 is a first-in-class off-the-shelf OncoMimics immunotherapy that combines three OncoMimics peptides that closely mimic IL13Ra2, BIRC5 and FOXM1.

Nouscom announced positive Phase I data of NOUS-209 for treatment of DMMR/MSI-H solid tumors. The drug is an off-the-shelf neoantigen cancer immunotherapy.

Transgene presented updated preliminary Phase I data on TG4050. The drug is an individualized neoantigen cancer vaccine.

AstraZeneca and Daiichi Sankyo presented data that demonstrated that Enhertu gave a 49% improvement in overall survival by more than six months compared to chemotherapy alone. The data was from the DESTINY-Brest04 study. Enhertu is a HER-2-directed therapy.

Gilead Sciences presented data from the Phase III TROPiCS-02 trial of Trodelvy (Sacituzumab govitecan-hziy) in heavily pre-treated HER+/HER2- metastatic breast cancer patients. It hit the primary endpoint of progression-free survival, showing a 34% reduction in the risk of disease progression or death.

Janssen, a Johnson & Johnson company, presented Phase III data of Imbruvica (ibrutinib) in lymphoma. The drug is a Bruton tyrosine kinase inhibitor. It reduced the risk of disease progression by 25% when combined with bendamustine-rituximab and rituximab in patients with newly diagnosed mantle cell lymphoma.

Pfizer presented data from the Phase III study of Ibrance (Palbociclib) in combination with letrozole. The drug is a first-line treatment for ER+, HER2- metastatic breast cancer, but in this study did not improve overall survival rate.

ImmunityBio announced new positive results from the pivotal Phase II/III study for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (QUILT 3032) and Phase II trial in advanced pancreatic cancer (QUILT 88). The data supported the company’s approach to activating NK cells and T cells for difficult-to-treat cancers.

VBI Vaccines presented new tumor response and overall survival data from the ongoing Phase IIa trial of VBI-1901. VBI-1901 is a cancer vaccine immunotherapy targeting recurrent glioblastoma.

Clovis Oncology announced data from the monotherapy arm of the Phase III ATHENA trial of Rubraca as first-line maintenance treatment for advanced ovarian cancer. The drug significantly improved PFS compared to placebo.

CEL-SCI Corporation presented an abstract and poster describing its leukocyte interleukin injection (LI) immunotherapy in advanced primary squamous cell carcinoma of the head and neck. Multikine (Leukocyte Interleukin, Injection) extended overall survival (OS) in patients with treatment-naive low-risk locally advanced primary squamous cell carcinoma of the head and neck.

Jazz Pharmaceuticals announced positive data from a Phase II/III study developed and run with the Children’s Oncology Group (COG). They evaluated the intramuscular administration of Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) in adult and pediatric patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who developed hypersensitivity to an E. coli-derived asparaginase. The data confirmed interim analysis presented in December 2021. It demonstrated that greater than 90% of patients in Cohort 1c receiving the IM dose three days per week hit nadir serum asparaginase activity (NSAA) levels greater than or equal to 0.1 IU/mL at 48 and 72 hours.

CARsgen Therapeutics presented study results for CT041, an autologous CAR T-cell candidate against the Claudin18.2 protein. They presented two posters, one with data from the multicenter Phase Ib CT041 trial in the U.S. for patients with advanced gastric and pancreatic adenocarcinoma, and the second was safety and preliminary efficacy data from the Phase Ib/II CT041 trial in China for advanced gastric/gastroesophageal junction adenocarcinoma. In the first, in a subgroup of patients, an objective response rate (ORR) of 60% was reported, with one patient achieving complete response (CR). Tumor shrinkage was seen in 80% of patients with stable disease. Median duration of response (mDOR) and progression-free survival (mPFS) was not reached. In the second study, the preliminary data suggested CT041 had manageable safety and tolerability with promising efficacy in patients with previously treated advanced GC/GEJ.

Ascentage Pharma released the latest results from a Phase Ib/II trial of the third-generation tyrosine kinase inhibitor olverembatinib in patients with metastatic gastrointestinal stromal tumor (GIST) who were resistant to or failed previous TKI treatment. The drug recently received approval in China for adults with TKI-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation.

Novartis announced results from a Phase II/III trial of Tafinlar (dabrafenib) and Mekinist (trametinib) in pediatric low-grade glioma (pLGG) patients with the BRAF V600 mutation. The drug combination outperformed chemotherapy, with an ORR of 47% compared to 11% for chemotherapy.

AlloVir announced preliminary, blinded data from an ongoing Phase II trial of posoleucel for treatment of BK viremia in adult kidney transplant recipients. The drug is an allogeneic, off-the-shelf, multi-virus-specific T cell therapy.

AtriCure treated the first patient in the HEAL-IST trial of AtriCure’s Isolator Synergy Clamp for treatment of drug-refractory patients diagnosed with Inappropriate Sinus Tachycardia (IST). The study involves a hybrid epicardial and endocardial procedure.

Engrail Therapeutics announced positive data from a Phase Ib trial of ENX-101 for focal epilepsy. ENX-101 is a subtype-selective GABA-A positive allosteric modulator.

Nascent Biotech completed the third cohort of doing patients for its Phase I trial for metastatic brain cancer. Pritumumab (PTB) is a natural human antibody that binds to cell surface vimentin (ectodomain vimentin, EDV), a protein expressed on the surface of epithelial cancers.

Apellis Pharmaceutical and Sobi dosed the first patient in the Phase III VALIANT study of pegcetacoplan in primary immune-complex membraneproliferative glomerulonephritis and C3 glomerulopathy. Pegcetacoplan is a targeted C3 therapy.

Kazia Therapeutics announced that a Phase II study led by the Alliance for Clinical Trials in Oncology has advanced the paxalisib arm to an expansion stage in breast cancer after completion of the pre-specified interim analysis. In the study, patients with breast metastases from breast, lung or other primary cancers were recruited and assigned to either receive Eli Lilly’s abemaciclib, Genentech’s entrectinib, or Kazia’s paxalisib.

Newron Pharmaceuticals announced encouraging interim results from the first 100 patients in its trial of evenamide as an add-on to an antipsychotic in patients with moderate to severe treatment-resistant schizophrenia who were not responding to current antipsychotic medication. Evenamide is an orally available New Chemical Entity that targets voltage-gated sodium channels.

Seres Therapeutics announced confirmatory results from ECOSPOR IV, an open-label study for SER-109 for prevention of recurrent C. difficile infection. SER-109 is an oral microbiome therapeutic. The therapy was well tolerated.

Concert Pharmaceuticals published safety and efficacy data from the Phase II trial of CTP-543. The drug is an investigational oral JAK inhibitor being evaluated for moderate to severe alopecia areata.

Moderna dosed the first participants in a Phase III trial of its seasonal influenza vaccine candidate, mRNA-1010. It expected to enroll about 6,000 adults in countries in the Southern Hemisphere.

Zealand Pharma presented data from the Phase I trial of dapiglutide. The drug is a GLP-1R/GLP-2R dual agonist being developed to treat obesity. It demonstrated dose dependent weight loss of up to 4.3% in body weight after only four weeks of treatment.

Aldeyra Therapeutics reported that its reproxalap hit the mark in the Phase III TRANQUILITY-2 study for dry eye disease. The drug showed statistical superiority for its two primary endpoints. Reproxalap is a first-in-class small-molecule modulator of reactive aldehyde species (RASP). RASP are elevated in ocular and systemic inflammatory disease.

Annexon released final data from its Phase II trial of ANX005 for Huntington’s disease. The drug demonstrated it has safely stabilized disease progression.

PMV Pharmaceuticals presented Phase I/II PINNACLE data of PC14586 in advanced solid tumors. The drug is a first-in-class, precision oncology, small molecule that targets the p53 Y220C mutation.

Genmab and Seagen reported their innovaTV 205 trial of Tovdak (tisotumab vedotin) in combination with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in recurrent or metastatic cervical cancer failed to hit the median durability of response endpoint at the average 19-month follow-up period.

ChemoCentryx announced interim results from its ongoing Phase I trial of CCX559 for advanced solid Tumors. The drug was demonstrated to be generally safe, with no dose-limiting toxicities.

eFFECTOR Therapeutics announced positive initial data from its Phase I/II trial of zotatifin in solid tumors. The drug is an eIF4A inhibitor.

Cue Biopharma reported initial results from a Phase I trial of CUE-101 with Merck’s Keytruda. It was found to be generally safe as a monotherapy as well. CUE-101 is a novel HPV16 E7-pHLA-IL2-Fc fusion protein.

Blue Earth Diagnostics completed patient accrual in its Phase III REVELATE trial of 18F-fluciclovine. The product is a PET imaging radiopharmaceutical being evaluated for possible use in detecting recurrent brain metastases after radiotherapy.

Gannex, a wholly owned company of Ascletis, received FDA clearance for a drug-drug interaction study of ASC42. The drug is an in-house developed, novel non-steroidal, selective, potent Farnesoid X receptor (FXR) agonist being developed to treat primary biliary cholangitis.

HMNC Brain Health with Develco pharma dosed the first patient in their second Phase II trial of KET01 for treatment-resistant depression. The drug is an oral prolonged-release ketamine.

Sonoma BioTherapeutics received clearance from the FDA to initiate a Phase I trial of SBT115301 for autoimmune diseases. The drug is an effector T cell-modulating biologic.

FibroGen completed patient enrollment of the Phase III LELANTOS-2 study of pamrevlumab in patients with ambulatory Duchenne muscular dystrophy (DMD). Pamrevlumab is a potential first-in-class antibody designed to inhibit CTGF.

Passage Bio received the greenlight for a Phase I trial of PBML04 for metachromatic leukodystrophy (MLD). The therapy is an adeno-associated virus-delivery gene therapy.

Prometheus Biosciences announced it has completed enrollment of the APOLLO-CD Phase IIa study of PRA023 in Crohn’s disease, and enrollment is on schedule in the Phase II trial of its ARTEMIS-UC study in ulcerative colitis, with completing of cohort 1 expected in the third quarter. PRA023 is an IgG1 humanized monoclonal antibody that blocks TNF-like ligand 1A.

Marinus Pharmaceuticals amended the protocol for its Phase III RAISE trial in refractory status epilepticus to expand eligibility criteria and patient recruitment. The study is evaluating ganaxolone (Ztalmy). The drug has been approved by the FDA for seizures associated with CDKL5 deficiency disorders in patients two years and older.

Alimera Sciences’ partner Ocumension Therapeutics received approval in China to launch a Phase III trial of fluocinolone acetonide intravitreal implant for diabetic macular edema. 

Biohaven Pharmaceutical presented 31 abstracts, including three late-breakers and three oral presentations at the AHS meeting. The showcase was full Phase III data for zavegepant nasal spray as acute treatment for migraine. It also presented data from a 52-week open label extension study of Nurtec (ODT) (rimegepant) of every other day preventive treatment of migraine and as an as-needed acute treatment. Zavegepant is a third-generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist. In a Phase II/III trial with more than 1000 patients receiving the drug, it demonstrated statistical superiority to placebo on the co-primary endpoints of 2-hour freedom from pain and freedom from a patient’s most troublesome symptoms, either nausea, photophobia or phonophobia. The Nurtec study demonstrated the drug was safe and effective and helped almost half of the patients achieve 100% reduction in monthly migraine days.

Teva Pharmaceuticals presented data from a subgroup analysis of the Phase IIIb FOCUS study detailing the use of the drug in patients with difficult-to-treat migraine and comorbid obesity.

Satsuma Pharmaceuticals presented five abstracts highlighting STS101 (dihydroergotamine (DHE) nasal powder) for migraine. The data presented includes long-term safety and tolerability of the drug from the Phase III trial, subject impression data, nasal safety data and more. The drug is being developed for acute treatment of migraine. It is a unique and proprietary nasal powder formulation of a well-established migraine treatment, DHE, dosed using the company’s proprietary nasal delivery device.

Takeda announced that TAK-003, it’s Dengue fever vaccine, prevented 84% of hospitalized dengue cases and 61% of symptomatic dengue cases. No important safety problems were observed.

Alnylam Pharmaceuticals announced positive topline results from its Phase II trial of cemdisiran for immunoglobulin A nephropathy (IgAN). The drug is an RNAi monotherapy.

Precision BioSciences announced data from a Phase I/IIa trial of PBCAR0191 for r/r aggressive lymphomas. The study demonstrated a 100% ORR and 73% CR as of May 31. The therapy is an allogeneic CAR-T therapy.

Adverum Biotechnologies announced new data from the OPTIC study of ADVM-022 in wet age-related macular degeneration. The therapy is a novel gene therapy.

Tryp Therapeutics announced the initial data readout for the first patient dosed in its Phase II STOP trial. It is evaluating TRP-8802 in patients with Binge Eating Disorder. The therapy is a psilocybin product.

Cend Therapeutics treated the first patient in the Phase IIb trial of CEND-1 for first-line metastatic pancreatic ductal adenocarcinoma. The drug modifies the tumor microenvironment by targeting tumor vasculature with an affinity for alpha-v integrins.

Lyndra Therapeutics dosed the first patient in its Phase I trial of oral biweekly ivermectin to fight malaria. The company’s LYNX drug delivery platform allows oral biweekly ivermectin possible.

Plague Profits: Vaccines, Part 1

In the U.S. and Europe, basically five companies have successfully brought COVID-19 vaccines to market: Pfizer and BioNTech, AstraZeneca with the University of Oxford, Johnson & Johnson’s Janssen division, and Moderna. This is just a brief look at what happened to these company’s revenues from 2019, prior to the COVID-19 pandemic, and the following two years. Revenues are not necessarily profits. More analysis on profitability and where some of this money comes from will be included in future posts.

Pfizer and BioNTech have been broken out separately. For Johnson & Johnson, the numbers represent just one of the mammoth company’s units, Pharmaceuticals.

One thing becomes clearly obvious. COVID-19 vaccines have brought in an incredible amount of money for all of these companies. Pfizer’s sales basically doubled since 2019, BioTech’s went from only $117.53 million in 2019 to $20.52 billion in 2021. AstraZeneca went from $24.384 billion in 2019 to $37.417 billion in 2021, and J&J’s Pharma sales climbed from $42.198 billion to $52.080 billion. Moderna’s COVID-19 vaccine is the company’s first commercial product (same as BioNTech). As a result, sales went from $60 million in 2019, which is basically for licensing fees, to $18.471 billion in 2021.

Pfizer

Revenue

2019                                        2020                                        2021

$40.905 billion                        $41.651 billion                        $81.288 billion

BioNTech

2019                                        2020                                        2021

$117.53 million (U.S.)            $521.46 million (U.S.)            $20.52 billion (U.S.)

AstraZeneca

2019                                        2020                                        2021

$24.384 billion (U.S.)             $26.617 billion (U.S.)             $37.417 billion (U.S.

J&J (Pharmaceutical Only)

2019                                        2020                                        2021

$42.198 billion                        $45.572 billion                        $52.080 billion

Moderna

2019                                        2020                                        2021

$60 million                             $803 million                           $18.471 billion