Frontera Insight No.05

FRONTERA

 INSIGHT

● Innovation ● Efficiency ● Integrity ● Rigor

2024.03

General  Issue No.05

Contents

Chief Editor ：

Managing Editor ：

Proofread ：

Contributors：

Maggie Xue

Jackie Peng

Sunny Han

Eileen Kenney, Jiayan He,

Jing Yu, Meng Li, Mandy Lu,

Qian Wang, Suping Zhao, 

Tingting Chen, Wan Fang,

Zhiyan Li, Yolanda Zhao

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Science Trivia - Visual Field Test

Clinical Application of AAV Gene Therapy in CVD

Science Class

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 CEO Foreword

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Vivo Pharmacology Team Profile

US-China Team Interaction

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Frontera Annual Summit China 2024

Company Events

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- Judgment of Calibration Instrument

- Expedited Pathways Help Drugs Develoment 

and Marketing

- About Chamber Equipment Validation

- Finance Alliance

Department Information

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- “Blind Box” - New Member of QC family

- The Humble Administrator's Garden

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- Our Anniversary

- Getting to Know New Faces in Frontera

- Employee Recognition - US

People in Frontera

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Adversity looms, but I stand tall

Fearless, resolute, I will not fall.

With every challenge, my spirit grows stronger

Determined to emerge victorious, ever longer.

Onward I march

Through obstacles, I will not bend.

For I know that victory awaits

On the other side of my fears, unshaken.

 The gentle breeze of spring heralds the arrival of a new chapter in 2024. Just as the Spring Festival films "You Only Live Once" and "Pegasus 2" embody our corporate culture's deep commitment to quality and speed, so too do we strive for excellence in every aspect of our work.

"High Quality" is our promise to patients, our relentless pursuit of excellence, and our unwavering belief in overcoming obstacles. On the other hand, "Speed" embodies our value of efficiency, reflecting our desire to surpass ourselves, our determination to execute tasks efficiently, and our insatiable hunger for success that keeps us competitive.

In recent years, China has seen significant enhancements in the speed, quality, and innovativeness of its biopharmaceutical industry. Innovation has evolved from a focus on quantity and speed through imitation to Me-better strategies, and now increasingly strives for Best/first-in-class potential.

As we all step out of this extended Spring Festival holiday, it's time for our company and each of our employees to pursue quality and speed in our work and business development. It's a long and difficult journey, but one we must undertake. Root down to accumulate and consolidate when the strong winds are blowing, we can achieve rapidly grow when the time is ripe. 

CEO Foreword

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『NEWS BRIEF』

Selected as one of the "Unicorn" cultivating enterprises in Suzhou in 2023

January 3, 2024, Frontera was successfully selected as one of the 2023 Suzhou “Unicorn” Cultivation Enterprises, which means that our innovation ability, development speed and growth potential have been recognized by industry.

Suzhou "Unicorn" Cultivation Enterprises are selected by Suzhou Science and Technology Bureau through a series of selection and evaluation of innovative enterprises with disruptive innovation, explosive growth, outstanding competitive advantages, and large output value in the future, which has become synonymous with innovation and development.

FT-002 Achieves Orphan Drug Designation from the U.S. FDA for Inherited Retinal Dystrophies

January 23, 2024 - Frontera Therapeutics announces that its pioneering AAV gene therapy product, FT-002, has received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of Inherited Retinal Dystrophies (IRD) caused by RPGR gene variants. 

Frontera’s study report on ” Case Studies of Resolving AAV Aggregation & Removing Empty Vectors ” presented in Gene Therapy for Rare Disorders 2024

On March 26-29, 2024, the 7th Gene Therapy for Rare Disorder 2024 was held in Boston, USA. Dr. Robert Hongxiang Lu, Senior Vice President of Frontera, is invited to attend and give presentation on the conference.

Details of the report are as follows:

• Report Title: Case Studies of Resolving AAV Aggregation & Removing Empty Vectors

• Report Category: Manufacturing- Addressing Key Upstream & Downstream Vector Production Challenges

The conference attracts many leading companies and technical experts from gene therapy industry. On March 27, similar reports will also be shared on “Upgrade Upstream Manufacturing to Improve Batch Productivity and Consistency” by experts at Rocket Pharmaceuticals and “Evolution of Downstream Manufacturing Process Design to Improve Productivity, Product Quality, and Process Consistency” by experts from Spark Therapeutics.

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Frontera News Brief

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『NEWS BRIEF』

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Our in vivo pharmacology team focuses on assessing the efficacy of our AAV-based therapies in animal models. Basically, we use animal models, primarily mouse models, as a tool to learn whether our innovative gene therapy drugs are safe and effective. Since many of our programs aim at treating diseases caused by genetic deficiency, we have frequently used genetically modified mouse models to inform us on the effectiveness of our drug candidates. Recently we made nice progress in advancing two of our cardiovascular programs (FT017 and F018) to the next stage of development candidate nomination/selection. In both programs, we have demonstrated that our AAV-based drug candidates successfully target cardiomyocytes and significantly improve cardiomyopathy in two distinct genetically modified mouse models. The team also recently accomplished a daunting job in shipping both mouse models to our China sites for IND-enabling studies. Currently our in vivo team operates at a laboratory vivarium space provided by Avastus Preclinical Services, an animal facility about 20 minutes away from our Bedford main site.

Vivo Pharmacology Team Profile

Left to right:： Deepthi Yedlapudi, Therese Salameh, Jingsong Cao

Currently we have three team members in the in vivo pharmacology:

Jingsong Cao – A seasoned pharmacologist and molecular biologist bringing in two decades of experience directing drug discovery programs in biopharmaceutical industry. Outside of work, he is an avid marathon runner and enjoys both playing and watching sports such as soccer and volleyball.

Therese Salameh – A highly skilled in vivo pharmacologist with two decades of experience working with animal models of neurodegeneration, metabolic and cardiovascular disease. In her free time, she cross country skis, plays pickleball and reads.

Deepthi Yedlapudi – Experienced molecular biologist and in vivo pharmacologist. Mom to a very active two-year-old son. Loves to cook and enjoys hikes when it’s not freezing cold outside.

We look forward to working with all of you at Frontera!

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『US-CHINA TEAM INTERACTION』

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『US-CHINA TEAM INTERACTION』

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『COMPANY EVENTS』

 Frontera Annual Summit  China 2024

 In the Spotlight Together, Behind the Scenes Collaboratively

Joyce Wang , Admin Dept.

On March 1, 2024, the 2024 Frontera Annual Summit was held in China, with a magnificent and splendid stage in front of the stage, behind which a group of staff members worked together and paid in silence. Today, let's take a look at the unknown behind-the-scenes story. 

As the saying goes: "One minute on the stage, ten years off the stage", presented on the stage of wonderful performance, is the performers day and night of intensive rehearsal, each program is worth the warmest applause.

Planners try to communicate and dock, "pick out details" and sometimes struggle for better stage effects, "arguing" from the left or right side of the stage, "research" etiquette to go on the left or right, and what the microphone transmission route is, perhaps only the preparators and those involved in it is known that some "careless" is actually "careful steps.".

Props, prizes, clothing, companion gifts procurement and payment arrival is also a matter of trouble; lighting, sound, stage, table, etc. are placed and installed in close proximity, and each background is carefully designed to fit the program. The music switching and lighting design of each program need to be controlled at all times in the background to ensure the smooth operation of the scene.

After the summit, the staff actively cleaned up the venue, methodically, and helped each other, and all worked together to leave the meeting smoothly, drawing a successful conclusion for the summit.

From the overall planning of the summit to the program rehearsal, to the end of the summit, serious, hardworking, professional and perseverance, each behind-the-scenes staff are doing their best to serve the entire summit with the fullest and warmest attitude. 

The hosts grasped the rhythm of the whole summit. In order to ensure the smooth progress of the summit, our hosts rehearsed, cooperated with the series of manuscripts, verbatim verbatim proofreading, and timely adjustment of problems found, and both hosts took out 200 points of seriousness. 

One month in advance, the Administration Department began to write a script for the opening video of the summit, polishing each frame repeatedly, repeatedly considering each sentence of subtitles, in order to give everyone a good picture, both warm and high-level opening video. 

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『COMPANY EVENTS』

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『SCIENCE CLASS』

Science Trivia - Visual Field Test

" Contraction of visual field", "Tubular visual field", "Central visual field", "size III and size V stimuli", those vocabularies were often mentioned in the discussion of FT-001/002 project , also mentioned by some patients or patient's relatives when they consulting whether to meet the eligibility criteria, In life, some friends also mentioned that they went to the hospital to do a visual field test, so what is the visual field test ? Today we're going to find out.

SPATIAL EXTENT OF THE VISUAL FIELD

The visual field of a person is defined as the area in which a person can see at a given moment relative to the direction of fixation, without head or eye movement (i.e., it defines the boundaries of the area beyond which nothing can be seen).

The visual field of one eye is called the monocular visual field (FIG 1). Its spatial extent in people with normal vision is limited by the facial anatomy of the person, with the eye socket, nose, brow and cheekbones, which outlines the limits of the visual field. On average, the monocular visual field extends from 60° nasally to ap- proximately 90° or more temporally, and from approxi- mately 60° superiorly to 70° inferiorly. In people with normal vision, the visual field is binoc- ular (FIG -1). This means that it contains input from both eyes, with integration and mapping of information from the two eyes, allowing for stereo acuity and depth perception. Visual information in the central 60 degrees of the visual field is processed by both eyes.

THE NORMAL VISUAL FIELD

*FIG 1

SENSITIVITY TO LIGHT IN THE VISUAL FIELD

The area in which a person can see (extent of the visual field) does not suffice to describe a person’s vision. It is also important to have a measure of sensitivity to light. But what is a person’s sensitivity to light? One can imagine a room in which 100 people are present. The room is dim, with an adjustable light bulb at its lowest level hanging from the ceiling. In that room, only a few people can see. As the light intensity of the bulb is in- creased, an increasing number of people will be able to see in the room. The people who could see even the very dim light bulb have a very high sensitivity to light, while the others have a lower sensitivity to light (FIG 2).

*FIG2

Wan Fang , CO Dept.

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『SCIENCE CLASS』

THE HILL OF VISION – A VISUALIZATION OF VISUAL FUNCTION

Sensitivity to light is not uniform across the spatial ex- tent of the visual field and depends on location within the visual field. For normal eyes and in typical daytime illumination, sensitivity is highest in the central area of the visual field and decreases gradually towards the pe- riphery. To visualize this, sensitivities across the visual field can be drawn as a three-dimensional graph, with the x- and y-axes representing the visual field locations and the z-axis representing the sensitivity to light. Since this representation resembles a hill, it is commonly re- ferred to as the hill of vision, which is a visualization of a person’s visual function. Areas within the hill of vision represent areas of seeing, and areas outside the hill of vi- sion represent areas of non-seeing (FIG 3).

MEASURING SENSITIVITY TO LIGHT ACROSS THE VISUAL FIELD

PERIMETRY ALLOWS QUANTIFICATION OF 

ABNORMAL SENSITIVITY TO LIGHT

Deviations from the normal hill of vision provide valu- able clues regarding visual field loss and the underlying pathologies. The pattern and shape of visual loss can be identified by investigating deviations from the normal hill of vision. Differences in the visual field between the two eyes can also be identified by inspecting deviations from the normal hill of vision. These deviations from normal can be either constrictions of the boundaries of the visual field, or depressions of sensitivity. Such depressions can be present throughout the visual field (widespread low- ering of sensitivity), or localized in specific areas of the visual field (scotomas). It is thus desirable to quantify a patient’s hill of vision with high accuracy and to identify its deviation from a normal hill of vision (FIG 4).

*FIG3

*FIG 4

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『SCIENCE CLASS』

THE PERIMETRIC TEST

This minimum light intensity that can be seen defines the patient’s sensitivity to light (i.e., the threshold between non-seeing and seeing) (FIG 5).

DISPLAY OF SENSITIVITY THRESHOLDS

THE DECIBEL SCALE USED IN PERIMETRY

In clinical practice, visual field information needs to be easy to interpret and should directly correspond to the clinical situation. For that purpose, perimetry employs the decibel scale, with its unit of measurement being the decibel (dB). The decibel range depends on perim- eter type and typically ranges from 0 dB to approxi- mately 32 dB in the fovea. A sensitivity threshold of 0 dB means that a patient is not able to see the most intense perimetric stimulus that the device can display, whereas values close to 32 dB represent normal foveal vision for a 20-year-old person (FIG 7).

*FIG 5

*FIG 7

The sensitivity threshold at the first test location provides the first data point to characterize the hill of vision (FIG 6A). To determine the patient’s hill of vision, the afore- mentioned procedure is then repeated at many locations across the visual field (FIG 6B). By connecting the sensitivity thresholds at all tested locations, a patient’s hill of vision can be drawn (FIG 6C).

*FIG 6

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PERIMETRIC TESTING HAS LOW RESOLUTION

From a practical point of view, however, it is nearly impossible to test each location within the visual field (spatial resolution) using each possible light intensity (luminance resolution). This would take too long to be useful in a clinical setting. Therefore, referring back to the example of the light bulb in a room, the dimmer only has a set number of discrete levels, such as high, medi- um and low, and there are only a few bulbs to illuminate the room (FIG 8).

For perimetry, this means that stimuli are presented at a fixed number of key locations and that only a limited number of light intensity levels are presented. This approach introduces inaccuracies in the perimetric test. In order to still be able to receive the information necessary for good clinical decision-making, a number of elaborate process- es are used in perimetry. This maximizes clinical infor- mation and offers a good trade-off between testing time and accuracy.

CHALLENGES IN VISUAL FIELD TESTING AND INTERPRETATION

*FIG 8

NORMAL SENSITIVITIES DEPEND ON AGE AND TEST LOCATION

As already illustrated in the section about the hill of vision, normal sensitivity thresholds depend on the test location and are higher at the center than in the pe- riphery. In addition, the normal hill of vision is affected by age. Normal sensitivity to light in decibels decreases approximately linearly with increasing age, beginning at the age of 20.1-3 Thus, the hill of vision of a 20-year-old is typically higher than the hill of vision of an 85-year-old person (FIG 9).

For these reasons, sensitivity thresholds are challenging to interpret directly in the clinic, because the representations of normal and abnormal values depend on testing- and patient-specific factors. For correct clinical assessment of sensitivity thresholds, a clinician would have to keep normal reference values in mind for all age groups and test locations, in order to correctly interpret the results.

*FIG 9

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PERIMETRY HAS OBJECTIVE AND SUBJECTIVE COMPONENTS

In the interest of simplicity, perimetry has been treated as a purely objective procedure, with exact measurements and distinct sensitivity thresholds at each test location. This is true for the equipment and the test conditions. However, there is a subjective element to perimetry, due to the subjectivity of the patients undergoing the test. As a result, there is always a certain amount of normal fluctuation both among different normal individuals, as well as between different measurements of the same individual over a short period of time. The accuracy of the test results is highly dependent on several factors, including the cooperation of the patients, their cognitive and physical abilities, and their decision criteria.4-6 If the patient does not understand the test, does not pay atten- tion or does not focus continuously on the central target, then the results of the test will be difficult to interpret. Additionally, some patients may be very conservative in their judgements, requiring a more intense stimulus for detection, while other patients may be liberal and accept a less intense stimulus for detection.

*FIG10

Therefore, distinct normative databases have been devel- oped for most modern perimeters and these databases are used to facilitate clinical visual field interpretation. Normative databases contain normal reference values for each age group and test location. They are used to compare any measured sensitivity threshold to Due to their ease of use, most representations in the Octopus perimeters are based on comparisons to the respective normative value for someone of that age. The calculated comparison to normal is clinically mean- ingful, as it relates directly to sensitivity loss (FIG 10).

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Clinical Application of AAV Gene Therapy in CVD

Lin Wang, Medical Dept.

Cardiovascular disease (CVD) refers to the disease of the heart and its blood vessels. The clinical manifestations include hypertension, coronary atherosclerotic heart disease, arrhythmia, myocardial disease, heart valve disease, etc. It is estimated that the number of patients with CVD in China is about 330 million, and the number is still growing. At present, treatment of heart disease is mainly restricted to conservative management and unable to cure the disease or reverse the disease progression.

With the development of life science and biomolecular technology, gene therapy may provide a "one-time, root-cause" treatment strategy for many complex and refractory diseases, including rare diseases, genetic diseases, and even common & chronic diseases, bearing the potential for a long lasting “cure”. Most cardiovascular diseases are polygenic and affected by environmental factors; gene therapy has the potential not only to cure inherited diseases with single gene defects, but also to modulate multifactorial diseases. AAV has become one of the preferred vectors for gene therapy due to its low immunogenicity, good safety profile, stable expression, strong target engagement, wide host range, and stable physical properties. In the treatment of cardiovascular diseases, compared with lentivirus vector (LV) and adenovirus vector (Ad), AAV can specifically target the heart tissue and stably express exogenous therapeutic genes persistently through the optimization of vector capsid and promoter design.

With the rapid development of molecular biology, AAV vector-mediated gene therapy has been used to deliver the corresponding functional target genes to the heart tissue for the expression of normal functional proteins in the molecular signaling pathways regulating the cardiac function. Relevant researches have been carried out in hereditary heart diseases, such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and acquired heart diseases (such as heart failure), which shew great potential in clinical settings.

At present, some research on AAV gene therapy has entered the clinical stage from basic research for CVD:

AskBio, a company focusing on development of AAV gene therapy, initiated a phase I study in 2019 to evaluate the safety and preliminary efficacy of AB-1002 in patients with advanced heart failure. AB-1002 is a rationally designed cardiotropic AAV vector that blocks the action of protein phosphatase 1 associated with CHF by introducing a therapeutic protein inhibitor 1. As per its preliminary clinical data, AB-1002 was safe and well tolerated. In some patients who had completed 12 months of follow-up, clinically meaningful improvements were observed in evaluations of left ventricular ejection fraction (LVEF), NYHA functional class, Minnesota Living with Cardiac Insufficiency questionnaire (MLHFQ), cardiopulmonary exercise testing, and 6-minute walk test (6MWT) at 12 months after treatment. It provides a potential new method for the treatment of congestive heart failure. This treatment is currently being studied in a phase II clinical trial.

Heart failure

TN-201 is an AAV gene-therapy product developed by Tenaya for the treatment of HCM caused by MYBPC3 mutations. TN-201 aims to provide a fully functional MYBPC3 gene to restore the normal level of MYBPC3 protein in cardiomyocytes, which has the potential to prevent disease progression and reverse the process of HCM by a single treatment. In pre-clinical studies, TN-201 prevented disease progression, reversed disease course and improved survival. FDA has approved IND application for TN-201, with the completion of the first phase I patient enrollment in October 2023.

Hypertrophic cardiomyopathy (HCM)

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TN-401 is another gene therapy product developed by Tenaya for the treatment of ARVC caused by PKP2 gene mutations. TN-401 is delivering functional PKP2 to cardiac cells, halting or even reversing disease progression by restoring normal protein levels. In November 2022, FDA granted orphan drug designation to TN-401, with phase Ib planned in the second half year of 2024.

Arrhythmogenic right ventricular Cardiomyopathy (ARVC)

In summary, the development of targeted gene delivery has laid the foundation for gene therapy of heart diseases. Although most of current applications of AAV-based gene therapy in cardiovascular diseases are still in the stage of basic research, some AAV gene therapy methods begun their initial exploration in human beings. It is believed that there will be more products entering the clinical stage and prove their clinical benefit in the near future, holding great promise for the treatment of refractory cardiovascular diseases.

Judgment of Calibration Instrument

Yolanda Zhao , EE Dept.

Calibration, defined in JJF 1001-2011 "National Metrology Technical Specifications of the People's Republic of China", is: a set of operations under specified conditions, the first step is to determine the relationship between the quantity provided by the measurement standard and the corresponding indication value, and the second part is to use this information to determine the relationship between the measurement result obtained by the indication value, where the measurement standard provides the quantity value and the corresponding indication value have measurement uncertainty. Clauses 90~95 of the Good Manufacturing Practice (GMP) have a total of six articles, which clarify the standard requirements for the calibration of pharmaceutical companies.

Calibration is a tedious and subtle civilian work, but it is also a rigorous, scientific aristocratic work. Every electronic scale in the supermarket has a need for calibration; Measurement in high-tech scientific research fields such as aviation and artificial intelligence also has a crucial need for calibration. For an effective measurement system, it is first necessary to determine which measurement items must be calibrated. The following is a brief introduction to the method of calibration judgment based on ISPE requirements and actual work.

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『DEPARTMENT INFORMATION』

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No need to be Calibrated

  For those that have no direct impact and are used for reference purposes only, calibration is not required.

Instruments that are not used to obtain accurate measurements, but only to obtain status information, do not need to be calibrated if they have no direct impact on the process. For example, the pressure gauge in the middle of the pipe of the purified water system is only used to check whether there is water pressure in the pipe, and there is no need to measure accurately, and the water pressure in the pipe is controlled by the pressure sensor at the front end, then the pressure gauge does not need to be measured.

In a word, a simple way: if the measurement data deviates, can the relevant processes be set up, monitored and operated correctly? One of answer to these questions is a no, the instrument must be calibrated; all are no, there is no need for calibration.

Must be Calibrated

1. Order No. 48 of the State Administration for Market Supervision of the People's Republic of China in 2019 "Catalogue of Measuring Instruments for Compulsory Management", in which all measuring instruments used for trade settlement, safety protection, medical and health care, and environmental monitoring shall be subject to compulsory verification in accordance with the law. For example, the pressure gauge used for the pressure measurement of the air compressor main pipe belongs to the strong inspection type of instrument and must be calibrated, usually called "strong inspection" or "verification".

2. Measurement items used to make release (quality) decisions. If the Nanodrop One microvolume spectrophotometer is used to detect the capsid protein fraction of the product, and the test results are used to determine whether the product is qualified, the Nanodrop One microvolume spectrophotometer must be calibrated.

3. Items used to set key process parameters. If the oxygen flow rate on the bioreactor affects the amount of oxygen in the reaction bag and will directly affect the growth state of the cells, the flow rate must be calibrated.

4. Projects for monitoring critical process (environmental) conditions. If the differential pressure and temperature and humidity monitoring in the EMS system are used to monitor the environment of the clean area, and the monitoring results are used to judge whether the clean area is qualified, the sensors in the EMS system must be calibrated.

5. Instruments used to measure supporting equipment, processes, design verification/verification/validation activities. For example, the Kaye temperature verification system is used to verify temperature control equipment such as refrigerators in the GMP production process, and the verification results are used to determine whether the equipment can be used for production, then the Kaye temperature verification system must be calibrated.

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『DEPARTMENT INFORMATION』

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Taking breakthrough therapy, conditional approval and priority review in China as examples, figure below intuitively illustrates how these expedited pathways shorten the time for drug development and marketing approval:

In addition to the expedited pathways mentioned above, you may have heard about orphan drug designation (ODD), orphan drugs are drugs intended for rare diseases, US ODD is designated for drugs that have shown some efficacy in treating rare diseases. ODD is not exactly an expedited pathway, while ODD can bring many benefits in US, such as 7 years of market exclusivity, exemption of registration fees for BLA applications (PDUFA, currently more than $3 million), 25% tax relief for clinical research fees, and so on. China will issue rare diseases list, drugs intended for rare diseases in this list will be orphan drug and there is no need to apply for ODD in China. Sponsor can apply for priority review for orphan drug so that the BLA review time will be shortened.

It should be noted that the expedited pathways described above do not exist independently, there is overlap and connection among them, one or more expedited pathways can be applied for one drug. The following figure shows the applicable application times of each expedited pathway, sponsor can develop a scientific, rational and forward-looking acceleration plan based on the characteristics of their products and indications.

Expedited Pathways Help Drugs Develoment and Marketing

Serina Cheng , RA and Project Management Dept.

It often takes more than 10 years for an innovative drug to be marketed. Both China and the United States have developed a variety of expedited pathways to accelerate drug development and marketing (see the table below). All pharmaceutical companies are actively exploring and designing expedited pathways suitable for their products. The front-runner hopes to " leave others in the dust ", and the fast follower hopes to "overtake the corner".

*Brief summary, refer to the corresponding regulations for details

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About Chamber Equipment Validation

Layne Chen , QA Dept.

In the pharmaceutical enterprises, chamber equipment is a common equipment, and its use is also very extensive. Relevant national regulations also stipulate that box equipment needs to be calibrated, especially GMP requirements chamber equipment needs to be validated to meet the production/inspection/storage needs of the pharmaceutical industry. So, in the chamber equipment validation, what do we need to pay attention to?

The main equipment parameter of the chamber equipment is temperature and humidity, then in the calibration, temperature and humidity is the parameter that needs to be calibrated, so the choice of temperature and humidity point is very important, and the choice of temperature and humidity point is mainly determined by its requirements, for example, after the constant temperature and humidity chamber is put into use, it basically uses a temperature point, such as 23℃/50%RH. So in the calibration, you can only measure this one temperature and humidity point, but some chamber equipment its role is used to heat or sterilization, such as the oven, then the range of calibration must include the temperature range of its entire sample, for example, the heated sample has 50℃, 100 ℃, 180 ℃, Then the calibrated temperature must include the entire range of 50-180 ℃, and at least 3 points. And some temperature and humidity chamber, its calibration temperature and humidity points are more, often include high temperature and high humidity, low temperature and low humidity, low temperature and high humidity, high temperature and low humidity and other special points.

For calibration, it is generally more concerned about the temperature deviation, uniformity, and stability. So, it is necessary to say what is temperature deviation, uniformity, and stability.

Temperature deviation: Chamber equipment measurement verification in a stable state, display the difference between the average temperature and the average measured temperature at the center point of the workspace.

Temperature uniformity: The measurement of the chamber equipment verifies the arithmetic average between the highest measured temperature and the lowest measured temperature in each test for a period of 30 minutes (every 2 minutes) in a steady state.

Temperature fluctuation: The measurement of the chamber equipment verifies that in a stable state, the temperature of the center point of the working space changes with the temperature point of time, that is, the temperature of the center point is half of the difference between the highest temperature and the lowest temperature measured within 30min (tested every 2min) (stability is to see the volatility).

In the validation process, the measurement time of the data is relatively long, generally can reach 24h and above, so in this case, the temperature deviation, uniformity and stability have more obvious performance, the more data involved in the calculation, the more can reflect the performance of the chamber, so in some long-term storage of samples in the environment chamber, such as refrigerator, drug storage chamber, validation is necessary. At the same time, the temperature pole in the chamber can be obtained through verification to guide the daily temperature monitoring.

Therefore, the calibration of the chamber equipment focuses on the accuracy of its temperature and humidity control, and the validation focuses on whether the performance of its actual long-term operation meets the expected results, and the test time is longer and the test conditions are more complex.

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『DEPARTMENT INFORMATION』

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『DEPARTMENT INFORMATION』

*KAYE Validator – Autoclave Validation

*Calibration – Validation

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『DEPARTMENT INFORMATION』

When I just joined the company, I was caught up with the first annual party held by the company after the epidemic. Looking forward to meeting " online friends " and colleagues from Suzhou city makes me excited while to perform on the stage as one of Finance members makes me nervous. Coming to the front of the stage in this annual party, Finance Department will get into an alliance with Clinical Operation Department to perform an adapted Hong Kong style song.

Before the party, we prepared the performance full of enthusiasm considered meanwhile how to increase the performance effect in echo to company's call of "Reducing Costs and Increasing Efficiency". Therefore, we prepared Hong Kong style shirts and decorations within the limited budget. Without changing the original style, we added Frontera elements in the lyrics, and strived to pull the effect of the performance. To entertain the audience with the performance at the annual meeting without affecting the daily work, we rehearsed passionately over and over again.

Finance Alliance

Pat Xue , FA Dept.

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『DEPARTMENT INFORMATIONA』

Finally, the annual party started on March 1st. After watching the wonderful performance prepared by colleagues from other departments, we could not help getting nervous. We encouraged each other and sang lyrics silently under the stage. When we stood in the spotlight of the stage, we were encouraged by the audience's enthusiastic applause to us. With everyone’s earnestness watching the show, we gain more and more confidence to perform excitedly and happily.

After the show ended, we could not calm down and were so eager to participate the following activities. The enthusiastic performance of colleagues, waves of lucky draw and red envelope rain brought the atmosphere of the annual meeting to a rousing climax.

As a new joiner of Frontera, I was so lucky to have the chance to take participate in the lively annual party. What’s more, I learned a lot from the presentation by department heads before the annual party and realized what Frontera was committed to achieve in gene therapy was so prospective while undertaking huge social responsibilities. I come to understand that all departments is an integration as a whole, and Finance Department needs to form an alliance with all other departments working together to make a brilliant tomorrow for Frontera.

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『PEOPLE IN FRONTERA』

4th Anniversary - US

3rd Anniversary - US

2nd Anniversary - US

Hongbin Xu - Principal Scientist

Hong Duan - Principal Scientist

Therese Salameh - Principal Scientist

Linrui Li- Senior Associate Scientist

Robert Lu - SVP, Technical Operations

Ting Yang  - Executive Director, Process Development

1st Anniversary - US

Brendan Leung - Associate Scientist II

Deepthi Yedlapudi - Sr. Scientist

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『PEOPLE IN FRONTERA』

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『PEOPLE IN FRONTERA』

1st Anniversary - CN

2nd Anniversary - CN

3rd Anniversary - CN

Hang Liu - QC Dept.

Qian Wang - EHS&Adimin Dept.

Joyce Wang -Admin Dept.

Suping Zhao -MF Dept.

Beibei Zhao - SC Dept.

Mandy Lu - FA Dept.

Hongda Zheng -MF Dept.

Tingting Chen -SC Dept.

Sunny Han - HR Dept.

Shuangfeng Chen - QC Dept.

Peng Yang - MF Dept.

Yanni Jiang - Medical Dept.

zhiyan Li - Clinical Development  Dept.

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My name is Shijia Song, I joined the Clinical Operation Department as CRA II on November 27, 2023. My hometown is Dalian, Liaoning province.I'm a courageous Sagittarius with a passion for traveling and the outdoors, my motto is“Don't worry about a thousand miles, the wind will come''.

Shijia Song

My name is Yanshu Xue. I joined the Finance Department on January 22,2024, as an Assistant Treasury Manager. My hometown is Puyang, Henan province. I am a romantic libra with a passion for reading and singing, my motto is“Realistic life, quality work”.

Pat Xue

I'm Jasmine Gao. I joined the company as Vice President of Cinical Development on February 22,2024. I am a Virgo in pursuit of perfection. I love living utensil and home settings, “More learning than adoption and favor accumulation than usage” is my motto.

Jasmie Gao

Getting to Know New Faces in Frontera - CN

Getting to Know New Faces in Frontera - US

I‘m Kathleen Steinbrecher, AP Specialist, joined Frontera on 11/21/23. I had attend Fisher College with a concentration in Business management and has several years’ experience in accounts payable in different industries but over the past 10 years her main focus has been working in pharmaceutical / biopharma. She has always had in interest in science and watching how drug discoveries can improve people’s health. On a personal note, Kathleen is married with 2 children and most recently gained a daughter-in-law with her son’s marriage. She likes to travel with her family, this past Spring she went to Maui, Hawaii. Loves to be outdoors and watches all sports (yes including golf). 

Kathleen Steinbrecher

Sarah Myers

I'm Sarah Myers, Senior HR Manager, joined Frontera on 03/04/24.I have over 9+ years of HR experience in the dynamic biotech/pharmaceutical space expertise spans across all facets of the HR function. Prior to joining Frontera Therapeutics, I was the Sr. HR Manager at Theseus Pharmaceuticals. I also worked at Allena Pharmaceuticals, Kura Oncology and Kala Pharmaceuticals, OvaScience, and Alkermes. I received my BA in English Communications, Writing, and Rhetoric form UMass Dartmouth. In my spare time,I like going skiing, going on hikes with her Morkie Mason, and traveling to new places around the world. 

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"Blind Box" - New Member of QC family

Jiayan He, QC Dept.

After nine months of waiting, amidst the anticipation of many aunties, the "little blind box" of Jie Hu from the QC family's biochemistry group was finally revealed. On Valentine's Day and also the fifth day of the Spring Festival which is the  day welcoming the God of Wealth in China, she welcomed her "Little God of Wealth".

Since the first day of hearing the good news, all the aunties in our department have been looking forward to this new little member. However, the pressure brought by the huge workload also made us a bit worried about this novice mother. Communication coordination and efficient cooperation were demonstrated to the fullest in these nine months. We did not miss any work while ensuring smooth prenatal check-ups, which truly showcases the spirit of Frontera.

We witnessed every day of the pregnancy, from the discomfort in the early stages, the fatigue in the middle, to the anxiety in the late stages. Every moment of the expectant mother was shared among the members of the QC family. We brainstormed ideas, experienced joy and worry together. As soon as the novice mother recovered, QC family members visited her, eager for her return. Of course, as veterans in the company, everyone also placed bets. Indeed, practice makes perfect, and in the end, most people's guess was correct—a baby boy. We wish the little one a happy and healthy growth.

It's wonderful to acknowledge that Amanda has made a positive impact on the downstream PD team at Frontera since joining in July 2023. Her hard work, quick learning ability, and dedication are commendable qualities. Being able to independently carry out Akta purification operations just within a few months of joining speaks volumes about her competence and adaptability. 

Her willingness to work extra hours when needed demonstrates a strong work ethic and commitment to achieving project goals (there were 15 purification runs almost every week during December, together with Jeff, Amanda had offered a great help in FT-017 process development). 

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Employee Recognition - US

In addition to work capability and ethics, Amanda's people skills, fitting into the team seamlessly, add another layer of value to her contributions. Team dynamics are crucial in a work environment, and Amanda's ability to integrate quickly enhances the overall team spirit. It's evident that the PD team feels fortunate to have Amanda as part of the Frontera family.

I would like to recognize Justin Isaacson for his efforts in providing timely testing support for all the programs and on-going studies.

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The Humble Administrator's Garden

Zhengquan Liu , MF Dept.

Spring is coming and the weather is getting warm.

March is the off-season to visit Suzhou gardens. I took a dozen members of my family to find out what it is that attracts so many tourists.

Since the wide-angle lens, always the noise of people occupies the picture, this time there can only be some of the humanistic features.

If it is said that the scholars of all dynasties prefer the Humble Administrator's Garden, it is not unrelated to the word "Gu Su"; The history of the garden has been deep in every hall pavilion, corridors and painted boats.

The history of the Humble Administrator's Garden can be traced back to The Three Kingdoms, when Wu Grand Governor Lu Ji's residence was here.

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『LIFE SHARING』

Ming Zhengde four years (1509), because of official frustration and return to the hometown of the imperial historian Wang Xianchen, to build a garden, from the Jin Dynasty Pan Yue "Xian Ju Fu" in "Building rooms and trees, happy here... sell vegetables for daily meals... also fool people for the administration", called "Humble Administrator's Garden".

After thousands of years, repair and renovation, too many stories piled up layer by layer, hidden under the craftsmen's brick by tile; The name of the pavilions in the garden deeply contains the Suzhou-style culture. The garden "Jan Shan Lou" is named after Tao Yuanming's poem "Picking chrysanthemums under the east hedge, leisurely seeing Nanshan".

Beautiful scenery and culture are intertwined, linger here cannot help with but feel that.

Everything in the world is like the past cloud, only fine views forever in the heart.

Address (Boston): One Patriot Park,Bedford, MA 01730,USA

Address (Shanghai): Unit 1001, 10th Floor, Building C,Chamtime Plaza,

Lane 2889, Jinke Road, Pudong New Area, Shanghai

Address (Suzhou): Unit 101, Building 8,No. 1 Xinze Road,Biobay, SIP,

Suzhou, Jiangsu Province.