BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

Krystal Biotech Company Highlights - Biotechnology company that specializes in gene therapy  - Utilizes proprietary HSV virus for delivery of genes to the target tissue - Multiple clinical programs and early research  pipeline including  dystrophic epidermolysis bullosa, autosomal recessive congenital ichthyosis & cystic fibrosis - Cash, cash equivalents, and short-term investments of $286.4 million as of September 30, 2020 Krystal Biotech, Inc. is a gene therapy company dedicated to developing and commercializing novel treatments for patients suffering from rare diseases. Krystal Biotech Platform Skin TARgeted Delivery platform, or STAR-D, that consists of an engineered HSV-1 vector and skin optimized gene transfer technology, suitable for introducing into the patient one or more therapeutic genes relevant to treating skin disease. The modified HSV-1 is a replication-defective, non-integrating viral vector that can efficiently penetrate a broad range of skin cells. ...

Precision BioSciences, Inc. Highlights - Clinical-stage biotechnology company dedicated to improving life  - Utilizes novel and proprietary ARCUS® genome editing platform - Developing Off-shelf Allogeneic CAR T cells & In vivo editing tools  - Net loss was $26.0 million - Approximately $104.1 million in cash and cash equivalents. Precision BioSciences, Inc. is a clinical-stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform. ARCUS is a highly specific and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the Company’s pipeline consists of multiple “off-the-shelf” CAR T immunotherapy clinical candidates and several in vivo gene correction therapy candidates to cure genetic and infectious diseases where no adequate treatments exist. Stock Information: (Nasdaq: DTIL)  AAPL Chart by TradingView Precision Bio...

Stoke Therapeutics Highlights  - Biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases  - Initiating Phase 1/2 study of its investigational drug STK-001 for treatment of  Dravet syndrome - Developing antisense oligonucleotide target for the treatment of  autosomal dominant optic atrophy (ADOA) caused by OPA1 protein deficiency - Company has $191.7 million in cash, cash equivalents and restricted cash Stoke Therapeutics (Nasdaq: STOK) is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near-normal levels. Stoke aims to develop the first precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of app...

Ionis Pharmaceuticals Highlights  - Ionis Pharmaceuticals, Inc. discovers and develops RNA-targeted therapeutics - Three approved commercial RNA targeted therapies: SPINRAZA, TEGSEDI, WAYLIVRA - Numerous in house and out liscened collaborative program - Net income of $5 million on a non-GAAP basis  - Cash equivalents, and short-term investments of more than $2.3 billion,   Learn More

The cut-point of the assay is the level of response of the assay that defines the sample response as positive or negative. Establishing the appropriate cut-point is critical to minimizing the risk of false-negative results. The screening cut points are determined by assaying a set of approximately 50 drug-naive individual serum samples over three days by two analysts for a total of six runs. Here, we describe the stepwise procedure to calculate the statistical cut point using the parametric and robust parametric method.  Steps for estimating Screening cut points 1) Compile the data from 50 drug-naive individuals assayed by two analysts over 3 days for a total of six days. (See template below)  2) Compute the log transformation of the assay signal and NC-normalized values for the data sets. Shankar et al 2008 recommend stepwise evaluation of non transformed and transformed data for establishing cut points. Based on our experience, the NC-normalized data are mostly suitable for...

Highlights of REGENXBIO - REGENXBIO is a leading clinical-stage biotechnology company  - Utilizes AAV viral vectors from the proprietary gene delivery platform - Therapeutic areas include retinal, metabolic, and neurodegenerative diseases - $290 million in cash, cash equivalents and marketable securities as of September 30, 2020 REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Our gene therapy product candidates are designed to deliver genes to cells to address genetic defects or to enable cells in the body to produce therapeutic proteins that are intended to impact disease. Through a single administration, our gene therapy product candidates are designed to provide long-lasting effects, potentially significantly altering the course of the disease and delivering improved patient outcomes. Stock Symbol: RGNX RGNX Chart by TradingView REGENXBIO Platform Utilizes AAV viral vectors from...

Lumasiran Lumasiran, an investigational, subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – in development for the treatment of adults and children with primary hyperoxaluria type 1 (PH1). Primary hyperoxaluria type 1 (PH1) PH1 is an ultra-rare orphan disease characterized by excessive oxalate production, which can lead to end-stage renal disease (ESRD) and other systemic complications. PH1 affects approximately 3.5 to 4 individuals per million in Europe and the United States. Heterogeneity in disease manifestation often contributes to delays in diagnosis, with a median time to diagnosis of approximately six years. PH1 leads to progressive kidney damage, and patients with advanced kidney disease require intensive dialysis to help filter waste products from their blood until they are able and eligible to receive a dual or sequential liver/kidney transplant, an invasive procedure associated with a high risk of ...

Highlights of AAV5-RPGR Gene Therapy Program - AAV5-RPGR is an investigational gene therapy product for RPGR-Associated X-Linked Retinitis Pigmentosa - Developed by Janssen (Johnson & Johnson) & MEIRAGTx - 12-months ongoing Phase 1 & 2 clinical trial data  were presented at AAO 2020 conference - Data showed that low and intermediate doses were well-tolerated -  Demonstrated statistically significant sustained or increased vision improvement across multiple metrics and modalities RPGR-Associated X-Linked Retinitis Pigmentosa In patients with XLRP, the photoreceptors that are responsible for converting light into signals that are sent to the brain, function poorly, leading to a degeneration of the retina and legal blindness in adulthood.  Gene Therapy Platform AAV5-RPGR is an investigational gene therapy product. It is delivered via subretinal injection targeting the central retina in the eye that was more affected at baseline. Regulatory Status of AAV5-RPGR Gen...

Highlights of Inclisiran Program - Inclisiran, an investigational cholesterol-lowering therapy, was added to the pipeline from the Novartis acquisition of The Medicines Company.  - Inclisiran recently received a positive CHMP opinion and recommendation for marketing authorization in Europe and is under review by the US Food and Drug Administration - Pooled data analyses from Phase III ORION-9, -10 and -11 showed that inclisiran consistently reduced low-density lipoprotein cholesterol (LDL-C) by approximately 51% in both male and female adult patients and in three age categories - Expected Approvals by End of 2020 or H1 2021 Inclisiran is a double-stranded siRNA, conjugated with GalNAc allowing for targeted uptake by hepatocytes. In hepatocytes, inclisiran silences PCSK9 expression, increasing LDL-C receptor recycling and expression on the hepatocyte cell surface, thereby increasing LDL-C uptake by hepatocytes and lowering LDL-C levels in the circulation. Inclisiran (ALN-PCSsc) is a...

ARU-1801 (Aruvant), Investigational Gene Therapy for Treatment of  Sickle Cell Disease: Regulatory Update Highlights of ARU-1801 Program: - Sickle Cell Disease is an inherited disorder that affects the production of hemoglobin - ARU-1801 is an investigational gene therapy developed by Aruvant Therapeutics - ARU-1801 received orphan designation by FDA & EMA - Company announced that the results from the phase 1/2 study (MOMENTUM) will be presented in ASH 2020 (December) Sickle cell disease affects 100,000 individuals in the United States, disproportionately affecting African Americans with one in 500 African Americans suffering from the disease. This inherited disease affects the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. The disease occurs when people inherit a mutation from each of their parents which causes people with SCD to not have normal, healthy adult hemoglobin in their red blood cells and instead have an abnormal...

Highlights of Valoctogene Raxaparvovec - Valoctocogene Roxaparvovec is an investigational gene therapy treatment for Hemophilia A developed by Biomarin - FDA issued the complete response letter requesting two years of durability data from the phase 3 study - EMA: Biomarin withdrew MMA application marketing authorization - Biomarin is awaiting one-year of Phase 3data for EMA resubmission and two years of Phase 3 data for FDA submission - If approved, it will become first-in-class gene therapy for the treatment of Severe Hemophilia A For Details Visit Valoctocogene Roxaparvovec Gene Therapy  for Severe Hemophilia A

Highlights - Eli-cel is a one-time investigational gene therapy for the treatment of Adrenoleukodystrophy - Marketing Authorization Application is submitted to EMA for commercial distribution in EU - Target   the BLA submission to the  U.S.  FDA for eli-cel in mid-2021. Long-term results from Phase 2/3 Starbeam study (ALD-102/LTF-304) suggest durability of response post eli-cel treatment - 31 out of 32 patients in ALD-102 had stable Neurologic Function Scores following treatment with Eli-cel  - No reports of graft failure, graft rejection, graft-versus-host disease (GVHD), replication-competent lentivirus, or insertional oncogenesis Adrenoleukodystrophy (ALD) ALD is a rare, X-linked metabolic disorder that is estimated to affect one in 21,000 male newborns worldwide. ALD is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently cause toxic accumulation of very-long-chain fatty acids (VLCFAs)...

Highlights  - Eladocagene exuparvovec is an investigational drug for the treatment of Aromatic L-amino acid decarboxylase (AADC) - Developed by PTC Therapeutics - Currently under EMA Review, the MMA application, decision delayed due to COVID - Decision Expected by Q2 2020 - Planned BLA submission to FDA by H1 2021 Aromatic L-amino acid decarboxylase (AADC) AADC deficiency is a rare genetic condition caused by a mutation in the dopa decarboxylase (DDC) gene, resulting in a lack of functioning AADC enzyme, which is responsible for the final step in the synthesis of key neurotransmitters dopamine and serotonin. AADC deficiency results in delays or failure to reach developmental milestones such as head control, sitting, standing, walking, or talking, low muscle tone (also known as muscular hypotonia), severe, seizure-like episodes involving involuntary eye movement (also known as oculogyric crises), autonomic abnormalities, and the need for life-long care. Given this neurologically dev...

Highlight - Lenadogene nolparvovec is an investigational drug for the treatment of LHON - Developed by GenSight Biologics - Currently under EMA Review, the MMA application was validated (Nov2020) - Decision Expected by Q2 2020 - Planned BLA submission to FDA by H2 2021 Leber Hereditary Optic Neuropathy (LHON) LHON is a rare, mitochondrial genetic disease, mainly affecting young males. The ND4 mutation results in the worst visual outcomes, with most patients becoming legally blind. There continues to be a high unmet medical need for the 800-1200 new ND4 LHON patients in Europe and the U.S. each year, particularly those who are struck blind in their prime working years. Lenadogene nolparvovec (tradename: LUMEVOQ®) is a recombinant adeno-associated viral vector, serotype 2 (rAAV2/2), containing a cDNA encoding the human wild-type mitochondrial NADH dehydrogenase 4 protein (ND4), which was specifically developed for the treatment of LHON associated with a mutation in the ND4 gene. Regulato...

TEGSEDI (inotersen) injection, for subcutaneous use Inotersen is an antisense oligonucleotide (ASO) inhibitor of human transthyretin (TTR) protein synthesis. TEGSEDI contains inotersen sodium as the active ingredient. CLINICAL PHARMACOLOGY Mechanism of Action Inotersen is an antisense oligonucleotide that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.  Pharmacodynamics The pharmacodynamic effects of TEGSEDI were evaluated in hATTR amyloidosis patients treated with 284 mg TEGSEDI via subcutaneous injection once weekly. With repeat dosing, the mean percent decreases from baseline in serum TTR from Week 13 to Week 65 of treatment ranged from 68% to 74% (median range: 75% to 79%). Similar TTR reductions were observed regardless of TTR mutation, sex, age, or race. Serum TTR is a carrier of retinol-binding protein, which is involved in the transport of vitamin A in...

Clinical Stage and Regulatory Timeline BMN-307 is an investigational gene transfer therapy intended to deliver its phenylalanine hydroxylase (PAH) gene to the liver tissue for the production of PAH enzyme protein. Biomarin is conducting a Phase 1/2 clinical trial (PHEARLESS) to evaluate the safety and efficacy of AAV-PAH gene therapy in subjects with PKU. On September 2020, Biomarin announced the dosing of the first patients in their clinical studies. Viral Vector and Gene Construct:  AAV5.-Liver-specific promoter- PAH. The PAH gene under the liver tissue-specific promoter that drives the expression in the liver tissue. AAV5 is an adeno-associated virus that has been previously used to deliver the gene into liver tissue and successful transgene expression.  Clinical Phase: Biomarin is currently conducting a Phas e 1 /2 (NCT04480567) open-label,  dose-escalation study to evaluate the safety and efficacy of BMN307 in PKU subjects with PAH deficiency . The propos...

Alnylam Pharmaceuticals, Inc., a biopharmaceutical company, focuses on discovering, developing, and commercializing RNA interference (RNAi) therapeutics. The company's pipeline of investigational RNAi therapeutics focus on genetic medicines, cardio-metabolic diseases, hepatic infectious diseases, and central nervous system/ocular diseases.  The commercially approved products include ONPATTRO (patisiran) , a lipid complex injection for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults; and  GIVLAARI for the treatment of adults with acute hepatic porphyria (AHP).  Platform RNAi therapies leverage two distinct approaches to enable the delivery of small interfering Ribonucleic Acid (siRNA): lipid nanoparticles (LNP) and GalNAc-conjugates Stock Symbol: ANLY Therapeutic Area (Late Stage) Hereditary ATTR amyloidosis, Hemophilia, Hypercholesterolemia, and Primary hyperoxaluria type 1 Q3 2020 Highlights  ONPATTRO® Global Net ...

Bamlanivimab is a neutralizing IgG1 monoclonal antibody that binds to the receptor-binding domain of the spike protein of SARS-CoV-2. The FDA has authorized the emergency use of bamlanivimab for the treatment of COVID-19 under an Emergency Use Authorization (EUA). " Based on a review of the topline data from the planned interim analysis of Trial J2W-MC-PYAB, also called BLAZE-1 (NCT04427501), an ongoing randomized, double-blind, placebo controlled, Phase 2 dose-finding trial of bamlanivimab monotherapy in outpatients with mild to moderate COVID-19, it is reasonable to believe that bamlanivimab may be effective for the treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40 kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization, and that, when used under the conditions described in this authorization, the known and potential...

EXONDYS 51 (eteplirsen) injection, for intravenous use Eteplirsen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. PMOs are synthetic molecules in which the five-membered ribofuranosyl rings found in natural DNA and RNA are replaced by a six-membered morpholino ring. Each morpholino ring is linked through an uncharged phosphorodiamidate moiety rather than the negatively charged phosphate linkage that is present in natural DNA and RNA. Each phosphorodiamidate morpholino subunit contains one of the heterocyclic bases found in DNA (adenine, cytosine, guanine, or thymine). Eteplirsen contains 30 linked subunits. The molecular formula of eteplirsen is C364H569N177O122P30 and the molecular weight is 10305.7 daltons. CLINICAL PHARMACOLOGY Mechanism of Action  Eteplirsen is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51...